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The Effects of Obesity on Immune Function and Pulmonary Host Defense

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Obesity and Lung Disease

Part of the book series: Respiratory Medicine ((RM,volume 19))

Abstract

Obesity is a common condition in developed nations known to increase the risk of cardiometabolic disease and is now implicated as a contributing factor to ailments of the lung. Once thought of as a passive vessel for the storage of excess lipids, adipose tissue is now appreciated for its role as an endocrine gland that secretes adipocyte-derived factors or adipokines known to regulate numerous physiologic functions. Leptin is the best characterized adipokine, and it has been shown to play a profound role in the regulation of innate and adaptive immunity in respiratory infections. The accumulation of excess adipose tissue in the obese has dramatic effects on the systemic immune response by contributing to a chronic state of low-grade inflammation and altering the host response to infection. Recent epidemiologic evidence and carefully controlled animal studies have demonstrated that excess adiposity impairs the host response against influenza infection. Whether or not obesity contributes to the risk of community-acquired or nosocomial pneumonia is not clear and requires further examination. Future elucidation of the mechanisms by which excess adiposity impairs immune function is warranted and would foster development of novel therapeutic strategies to treat pulmonary infections in obese patients.

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References

  1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010;303(3):235–41.

    PubMed  CAS  Google Scholar 

  2. Doyle SL, Lysaght J, Reynolds JV. Obesity and post-operative complications in patients undergoing non-bariatric surgery. Obes Rev. 2010;11(12):875–86.

    PubMed  CAS  Google Scholar 

  3. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377(9765):557–67.

    PubMed  Google Scholar 

  4. Bochicchio GV, Joshi M, Bochicchio K, Nehman S, Tracy JK, Scalea TM. Impact of obesity in the critically ill trauma patient: a prospective study. J Am Coll Surg. 2006;203(4):533–8.

    PubMed  Google Scholar 

  5. Intensive-care patients with severe novel influenza A (H1N1) virus infection – Michigan, June 2009. MMWR Morb Mortal Wkly Rep. 2009;58(27):749–52.

    Google Scholar 

  6. Newell MA, Bard MR, Goettler CE, Toschlog EA, Schenarts PJ, Sagraves SG, et al. Body mass index and outcomes in critically injured blunt trauma patients: weighing the impact. J Am Coll Surg. 2007;204(5):1056–61. discussion 62–4.

    PubMed  Google Scholar 

  7. Yaegashi M, Jean R, Zuriqat M, Noack S, Homel P. Outcome of morbid obesity in the intensive care unit. J Intensive Care Med. 2005;20(3):147–54.

    PubMed  Google Scholar 

  8. Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res. 2003;11(4):525–31.

    PubMed  CAS  Google Scholar 

  9. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121(6):2111–7.

    PubMed  CAS  Google Scholar 

  10. Fuhrman C, Bonmarin I, Bitar D, Cardoso T, Duport N, Herida M, et al. Adult intensive-care patients with 2009 pandemic influenza A (H1N1) infection. Epidemiol Infect. 2010;26:1–8.

    Google Scholar 

  11. Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory phenotype of perivascular adipocytes. Circ Res. 2009;104(4):541–9.

    PubMed  CAS  Google Scholar 

  12. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97.

    PubMed  CAS  Google Scholar 

  13. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46(11):2347–55.

    PubMed  CAS  Google Scholar 

  14. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12): 1796–808.

    PubMed  CAS  Google Scholar 

  15. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107.

    PubMed  CAS  Google Scholar 

  16. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. Obesity in C57BL/6 J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond). 2008;32(3):451–63.

    CAS  Google Scholar 

  17. Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, et al. Obesity- associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621–37.

    PubMed  CAS  Google Scholar 

  18. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–30.

    PubMed  CAS  Google Scholar 

  19. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84.

    PubMed  CAS  Google Scholar 

  20. Odegaard JI, Chawla A. Alternative macrophage activation and metabolism. Annu Rev Pathol. 2011;6:275–97.

    PubMed  CAS  Google Scholar 

  21. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914–20.

    PubMed  CAS  Google Scholar 

  22. Liu J, Divoux A, Sun J, Zhang J, Clement K, Glickman JN, et al. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med. 2009;15(8):940–5.

    PubMed  CAS  Google Scholar 

  23. Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci. 2011;108(37):15324–9.

    PubMed  CAS  Google Scholar 

  24. Tilg H, Moschen AR. Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clin Sci (Lond). 2008;114(4):275–88.

    CAS  Google Scholar 

  25. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996;271(18):10697–703.

    PubMed  CAS  Google Scholar 

  26. Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R, et al. Sfrp5 is an anti- inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010;329(5990):454–7.

    PubMed  CAS  Google Scholar 

  27. Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007;48(6):1253–62.

    PubMed  CAS  Google Scholar 

  28. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    PubMed  CAS  Google Scholar 

  29. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763–70.

    PubMed  CAS  Google Scholar 

  30. Bergen HT, Cherlet TC, Manuel P, Scott JE. Identification of leptin receptors in lung and isolated fetal type II cells. Am J Respir Cell Mol Biol. 2002;27(1):71–7.

    PubMed  CAS  Google Scholar 

  31. Bellmeyer A, Martino JM, Chandel NS, Scott Budinger GR, Dean DA, Mutlu GM. Leptin resistance protects mice from hyperoxia-induced acute lung injury. Am J Respir Crit Care Med. 2007;175(6):587–94.

    PubMed  CAS  Google Scholar 

  32. Bruno A, Pace E, Chanez P, Gras D, Vachier I, Chiappara G, et al. Leptin and leptin receptor expression in asthma. J Allergy Clin Immunol. 2009;124(2):230–7.

    PubMed  CAS  Google Scholar 

  33. Mancuso P, Peters-Golden M, Goel D, Goldberg J, Brock TG, Greenwald-Yarnell M, et al. Disruption of leptin receptor-stat3 signaling enhances leukotriene production and pulmonary host defense against pneumococcal pneumonia. J Immunol. 2011;186(2):1081–90.

    PubMed  CAS  Google Scholar 

  34. La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4: 371–9.

    PubMed  Google Scholar 

  35. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006;6(10):772–83.

    PubMed  CAS  Google Scholar 

  36. Bruno A, Conus S, Schmid I, Simon HU. Apoptotic pathways are inhibited by leptin receptor activation in neutrophils. J Immunol. 2005;174(12):8090–6.

    PubMed  CAS  Google Scholar 

  37. Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol. 1999;194:6–11.

    PubMed  CAS  Google Scholar 

  38. Zarkesh-Esfahani H, Pockley AG, Wu Z, Hellewell PG, Weetman AP, Ross RJM. Leptin indirectly activates human neutrophils via induction of TNF-α. J Immunol. 2004;172(3): 1809–14.

    PubMed  CAS  Google Scholar 

  39. Caldefie-Chezet F, Poulin A, Tridon A, Sion B, Vasson MP. Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J Leukoc Biol. 2001;69(3):414–8.

    PubMed  CAS  Google Scholar 

  40. Moore SI, Huffnagle GB, Chen GH, White ES, Mancuso P. Leptin modulates neutrophil phagocytosis of Klebsiella pneumoniae. Infect Immun. 2003;71(7):4182–5.

    PubMed  CAS  Google Scholar 

  41. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T- cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897–901.

    PubMed  CAS  Google Scholar 

  42. Gainsford T, Willson TA, Metcalf D, Handman E, McFarlane C, Ng A, et al. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci USA. 1996;93(25):14564–8.

    PubMed  CAS  Google Scholar 

  43. Mancuso P, Gottschalk A, Phare SM, Peters-Golden M, Lukacs NW, Huffnagle GB. Leptin- deficient mice exhibit impaired host defense in gram-negative pneumonia. J Immunol. 2002;168(8):4018–24.

    PubMed  CAS  Google Scholar 

  44. Mancuso P, Canetti C, Gottschalk A, Tithof PK, Peters-Golden M. Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2γ) protein expression. Am J Physiol Lung Cell Mol Physiol. 2004;287:L497–502.

    PubMed  CAS  Google Scholar 

  45. Raso GM, Pacilio M, Esposito E, Coppola A, Di Carlo R, Meli R. Leptin potentiates IFN- gamma-induced expression of nitric oxide synthase and cyclo-oxygenase-2 in murine macrophage J774A.1. Br J Pharmacol. 2002;137(6):799–804.

    PubMed  CAS  Google Scholar 

  46. Claycombe K, King LE, Fraker PJ. A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci USA. 2008;105(6):2017–21.

    PubMed  CAS  Google Scholar 

  47. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol. 2005;174(11):6820–8.

    PubMed  CAS  Google Scholar 

  48. Mattioli B, Straface E, Matarrese P, Quaranta MG, Giordani L, Malorni W, et al. Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin. FASEB J. 2008;22(6):2012–22.

    PubMed  CAS  Google Scholar 

  49. Tian Z, Sun R, Wei H, Gao B. Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun. 2002;298(3):297–302.

    PubMed  CAS  Google Scholar 

  50. Bruno A, Chanez P, Chiappara G, Siena L, Giammanco S, Gjomarkaj M, et al. Does leptin play a cytokine-like role within the airways of COPD patients? Eur Respir J. 2005;26(3): 398–405.

    PubMed  CAS  Google Scholar 

  51. Vernooy JH, Drummen NE, van Suylen RJ, Cloots RH, Moller GM, Bracke KR, et al. Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers. Thorax. 2009;64(1):26–32.

    PubMed  CAS  Google Scholar 

  52. Broekhuizen R, Vernooy JH, Schols AM, Dentener MA, Wouters EF. Leptin as local inflammatory marker in COPD. Respir Med. 2005;99(1):70–4.

    PubMed  CAS  Google Scholar 

  53. Mancuso P, Huffnagle GB, Olszewski MA, Phipps J, Peters-Golden M. Leptin corrects host defense defects following acute starvation in murine pneumococcal pneumonia. Am J Respir Crit Care Med. 2006;173(Jan 15):212–8.

    PubMed  CAS  Google Scholar 

  54. Faggioni R, Fantuzzi G, Fuller J, Dinarello CA, Feingold KR, Grunfeld C. IL-1 beta mediates leptin induction during inflammation. Am J Physiol. 1998;274(1 Pt 2):R204–8.

    PubMed  CAS  Google Scholar 

  55. Shore S, Schwartzman I, Mellema M, Flynt L, Imrich A, Johnston R. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol. 2005;115:103–9.

    PubMed  CAS  Google Scholar 

  56. Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol. 2008;121(5):1087–93. quiz 94–5.

    PubMed  Google Scholar 

  57. Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin–the classical, resistin–the controversical, adiponectin–the promising, and more to come. Best Pract Res. 2005;19(4):525–46.

    CAS  Google Scholar 

  58. Kawamoto R, Tabara Y, Kohara K, Miki T, Ohtsuka N, Kusunoki T, et al. Smoking status is associated with serum high molecular adiponectin levels in community-dwelling Japanese men. J Atheroscler Thromb. 2010;17(4):423–30.

    PubMed  CAS  Google Scholar 

  59. Shore SA, Terry RD, Flynt L, Xu A, Hug C. Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol. 2006;118(2): 389–95.

    PubMed  CAS  Google Scholar 

  60. Medoff BD, Okamoto Y, Leyton P, Weng M, Sandall BP, Raher MJ, et al. Adiponectin- deficiency Increases allergic airway inflammation and pulmonary vascular remodeling. Am J Respir Cell Mol Biol. 2009;41(4):397–406.

    PubMed  CAS  Google Scholar 

  61. Yamaguchi N, Argueta JG, Masuhiro Y, Kagishita M, Nonaka K, Saito T, et al. Adiponectin inhibits Toll-like receptor family-induced signaling. FEBS Lett. 2005;579(30):6821–6.

    PubMed  CAS  Google Scholar 

  62. Yokota T, Meka CSR, Medina KL, Igarashi H, Comp PC, Takahashi M, et al. Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest. 2002;109(10):1303–10.

    PubMed  CAS  Google Scholar 

  63. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000;96(5):1723–32.

    PubMed  CAS  Google Scholar 

  64. Summer R, Little FF, Ouchi N, Takemura Y, Aprahamian T, Dwyer D, et al. Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2008;294(6):L1035–42.

    PubMed  CAS  Google Scholar 

  65. Miller M, Cho JY, Pham A, Ramsdell J, Broide DH. Adiponectin and functional adiponectin receptor 1 are expressed by airway epithelial cells in chronic obstructive pulmonary disease. J Immunol. 2009;182(1):684–91.

    PubMed  CAS  Google Scholar 

  66. Sowers MR, Wildman RP, Mancuso P, Eyvazzadeh AD, Karvonen-Gutierrez CA, Rillamas-Sun E, et al. Change in adipocytokines and ghrelin with menopause. Maturitas. 2008;59(2):149–57.

    PubMed  CAS  Google Scholar 

  67. Uji Y, Yamamoto H, Tsuchihashi H, Maeda K, Funahashi T, Shimomura I, et al. Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality. Surgery. 2009;145(5):550–7.

    PubMed  Google Scholar 

  68. Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117(2):375–86.

    PubMed  CAS  Google Scholar 

  69. Saijo S, Nagata K, Nakano Y, Tobe T, Kobayashi Y. Inhibition by adiponectin of IL-8 production by human macrophages upon coculturing with late apoptotic cells. Biochem Biophys Res Commun. 2005;334(4):1180–3.

    PubMed  CAS  Google Scholar 

  70. Nakanishi K, Takeda Y, Tetsumoto S, Iwasaki T, Tsujino K, Kuhara H, et al. Involvement of endothelial apoptosis underlying chronic obstructive pulmonary disease-like phenotype in adiponectin-null mice: implications for therapy. Am J Respir Crit Care Med. 2011;183(9):1164–75.

    PubMed  CAS  Google Scholar 

  71. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007;53(1):34–41.

    PubMed  CAS  Google Scholar 

  72. Catalán V, Gómez-Ambrosi J, Rodríguez A, Ramírez B, Silva C, Rotellar F, et al. Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans. J Mol Med. 2009;87(8): 803–13.

    PubMed  Google Scholar 

  73. Chan YR, Liu JS, Pociask DA, Zheng M, Mietzner TA, Berger T, et al. Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J Immunol. 2009;182(8):4947–56.

    PubMed  CAS  Google Scholar 

  74. Wu H, Santoni-Rugiu E, Ralfkiaer E, Porse B, Moser C, Hoiby N, et al. Lipocalin 2 is protective against E. coli pneumonia. Respir Res. 2010;11(1):96.

    PubMed  Google Scholar 

  75. Corrales-Medina VF, Valayam J, Serpa JA, Rueda AM, Musher DM. The obesity paradox in community-acquired bacterial pneumonia. Int J Infect Dis. 2011;15(1):e54–7.

    PubMed  Google Scholar 

  76. Baik I, Curhan GC, Rimm EB, Bendich A, Willett WC, Fawzi WW. A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women. Arch Intern Med. 2000;160(20):3082–8.

    PubMed  CAS  Google Scholar 

  77. Womack J, Tien PC, Feldman J, Shin JH, Fennie K, Anastos K, et al. Obesity and immune cell counts in women. Metabolism. 2007;56(7):998–1004.

    PubMed  CAS  Google Scholar 

  78. O’Rourke R, Kay T, Scholz M, Diggs B, Jobe B, Lewinsohn D, et al. Alterations in T-cell subset frequency in peripheral blood in obesity. Obes Surg. 2005;15(10):1463–8.

    PubMed  Google Scholar 

  79. Tanaka S, Isoda F, Ishihara Y, Kimura M, Yamakawa T. T lymphopaenia in relation to body mass index and TNF-alpha in human obesity: adequate weight reduction can be corrective. Clin Endocrinol (Oxf). 2001;54(3):347–54.

    CAS  Google Scholar 

  80. Kim JA, Park HS. White blood cell count and abdominal fat distribution in female obese adolescents. Metabolism. 2008;57(10):1375–9.

    PubMed  CAS  Google Scholar 

  81. Nieman DC, Henson DA, Nehlsen-Cannarella SL, Ekkens M, Utter AC, Butterworth DE, et al. Influence of obesity on immune function. J Am Diet Assoc. 1999;99:294–9.

    PubMed  CAS  Google Scholar 

  82. Nieman DC, Nehlsen-Cannarella SI, Henson DA, Butterworth DE, Fagoaga OR, Warren BJ, et al. Immune response to obesity and moderate weight loss. Int J Obes Relat Metab Disord. 1996;20(4):353–60.

    PubMed  CAS  Google Scholar 

  83. Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA, et al. Obesity accelerates thymic aging. Blood. 2009;114(18):3803–12.

    PubMed  CAS  Google Scholar 

  84. Lynch LA, O’Connell JM, Kwasnik AK, Cawood TJ, O’Farrelly C, O’Shea DB. Are natural killer cells protecting the metabolically healthy obese patient? Obesity (Silver Spring). 2009;17(3):601–5.

    CAS  Google Scholar 

  85. O’Shea D, Cawood TJ, O’Farrelly C, Lynch L. Natural killer cells in obesity: impaired ­function and increased susceptibility to the effects of cigarette smoke. PLoS One. 2010;5(1):e8660.

    PubMed  Google Scholar 

  86. Chandra RK, Kutty KM. Immunocompetence in obesity. Acta Paediatr Scand. 1980;69(1): 25–30.

    PubMed  CAS  Google Scholar 

  87. Palmblad J, Hallberg D, Engstedt L. Polymorphonuclear (PMN) function after small intestinal shunt operation for morbid obesity. Br J Haematol. 1980;44(1):101–8.

    PubMed  CAS  Google Scholar 

  88. Zaldivar F, McMurray RG, Nemet D, Galassetti P, Mills PJ, Cooper DM. Body fat and circulating leukocytes in children. Int J Obes (Lond). 2006;30(6):906–11.

    CAS  Google Scholar 

  89. Dossett LA, Dageforde LA, Swenson BR, Metzger R, Bonatti H, Sawyer RG, et al. Obesity and site-specific nosocomial infection risk in the intensive care unit. Surg Infect (Larchmt). 2009;10(2):137–42.

    Google Scholar 

  90. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N Engl J Med. 2009;361(20):1935–44.

    PubMed  CAS  Google Scholar 

  91. Weber DJ, Rutala WA, Samsa GP, Santimaw JE, Lemon SM. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA. 1985;254(22):3187–9.

    PubMed  CAS  Google Scholar 

  92. Weber DJ, Rutala WA, Samsa GP, Bradshaw SE, Lemon SM. Impaired immunogenicity of hepatitis B vaccine in obese persons. N Engl J Med. 1986;314(21):1393.

    PubMed  CAS  Google Scholar 

  93. Sheridan PA, Paich HA, Handy J, Karlsson EA, Hudgens MG, Sammon AB, et al. Obesity is associated with impaired immune response to influenza vaccination in humans. Int J Obes (Lond). 2011;1–6.

    Google Scholar 

  94. Vaillant L, La Ruche G, Tarantola A, Barboza P. Epidemiology of fatal cases associated with pandemic H1N1 influenza 2009. Euro Surveill. 2009;14(33):1–6.

    Google Scholar 

  95. Jamieson D, Honein M, Rasmussen S, Williams J, Swerdlow D, Biggerstaff M, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009;374:451–8.

    PubMed  Google Scholar 

  96. Hanslik T, Boelle PY, Flahault A. Preliminary estimation of risk factors for admission to intensive care units and for death in patients infected with A(H1N1)2009 influenza virus, France, 2009–2010. PLoS Curr. 2010; 2:RRN1150.

    Google Scholar 

  97. Naseem A, Satti S, Khan MA, Saeed W. A clinical account of hospitalized 2009 pandemic influenza A (H1N1) cases. J Coll Physicians Surg Pak. 2011;21(2):97–102.

    PubMed  Google Scholar 

  98. La Ruche G, Tarantola A, Barboza P, Vaillant L, Gueguen J, Gastellu-Etchegorry M. The 2009 pandemic H1N1 influenza and indigenous populations of the Americas and the Pacific. Euro Surveill 2009;14(42):1–6.

    Google Scholar 

  99. Gill JR, Sheng ZM, Ely SF, Guinee DG, Beasley MB, Suh J, et al. Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections. Arch Pathol Lab Med. 2010;134(2):235–43.

    PubMed  Google Scholar 

  100. Fezeu L, Julia C, Henegar A, Bitu J, Hu FB, Grobbee DE, et al. Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta-analysis. Obes Rev. 2011;12:653–659.

    Google Scholar 

  101. Dominguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, de la Torre A, et al. Critically Ill patients with 2009 influenza A(H1N1) in Mexico. JAMA. 2009;302(17):1880–7.

    PubMed  CAS  Google Scholar 

  102. Jhung MA, Swerdlow D, Olsen SJ, Jernigan D, Biggerstaff M, Kamimoto L, et al. Epidemiology of 2009 pandemic influenza A (H1N1) in the United States. Clin Infect Dis. 2011;52(suppl 1):S13–26.

    PubMed  Google Scholar 

  103. Fuhrman C, Bonmarin I, Paty AC, Duport N, Chiron E, Lucas E, et al. Severe hospitalised 2009 pandemic influenza A(H1N1) cases in France, 1 July-15 November 2009. Euro Surveill. 2010;15(2):17–21.

    Google Scholar 

  104. Sigurdsson GH, Moller AD, Kristinsson B, Gudlaugsson O, Karason S, Sigurdsson SE, et al. Intensive care patients with influenza A (H1N1) infection in Iceland 2009. Laeknabladid. 2010;96(2):83–90.

    PubMed  Google Scholar 

  105. Mayoral Cortes JM, Ruiz Fernandez J, Pachon Diaz J, Navarro Mari JM, Puell Gomez L, Perez Morilla E, et al. Infection by the pandemic virus (H1N1) 2009 in Andalusia. Rev Esp Salud Publica. 2010;84(5):517–28.

    PubMed  Google Scholar 

  106. Dee S, Jayathissa S. Clinical and epidemiological characteristics of the hospitalised patients due to pandemic H1N1 2009 viral infection: experience at Hutt Hospital, New Zealand. N Z Med J. 2010;123(1312):45–53.

    PubMed  Google Scholar 

  107. Gauzere BA, Bussienne F, Bouchet B, Jabot J, Roussiaux A, Drouet D, et al. Severe cases of A (H1N1)v2009 infection in Reunion Island in 2009 and 2010. Bull Soc Pathol Exot. 2011;104(2):97–104.

    PubMed  Google Scholar 

  108. Cardenosa N, Rodes A, Follia N, Plasencia E, Lafuente S, Arias C, et al. Epidemiological analysis of severe hospitalized 2009 pandemic influenza A (H1N1) cases in Catalonia, Spain. Hum Vaccin. 2011;7:226–9.

    PubMed  Google Scholar 

  109. Rivera Claros R, Marin V, Castillo-Duran C, Jara L, Guardia S, Diaz N. Nutritional status and clinical evolution of hospitalized Chilean infants with infection by respiratory syncytial virus (RSV). Arch Latinoam Nutr. 1999;49(4):326–32.

    PubMed  CAS  Google Scholar 

  110. Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006;6(7):438–46.

    PubMed  Google Scholar 

  111. LaCroix AZ, Lipson S, Miles TP, White L. Prospective study of pneumonia hospitalizations and mortality of U.S. older people: the role of chronic conditions, health behaviors, and nutritional status. Public Health Rep. 1989;104(4):350–60.

    PubMed  CAS  Google Scholar 

  112. Inoue Y, Koizumi A, Wada Y, Iso H, Watanabe Y, Date C, et al. Risk and protective factors related to mortality from pneumonia among middleaged and elderly community residents: the JACC Study. J Epidemiol. 2007;17(6):194–202.

    PubMed  Google Scholar 

  113. Jedrychowski W, Maugeri U, Flak E, Mroz E, Bianchi I. Predisposition to acute respiratory infections among overweight preadolescent children: an epidemiologic study in Poland. Public Health. 1998;112(3):189–95.

    PubMed  CAS  Google Scholar 

  114. Choban PS, Heckler R, Burge JC, Flancbaum L. Increased incidence of nosocomial infections in obese surgical patients. Am Surg. 1995;61(11):1001–5.

    PubMed  CAS  Google Scholar 

  115. Canturk Z, Canturk NZ, Cetinarslan B, Utkan NZ, Tarkun I. Nosocomial infections and ­obesity in surgical patients. Obes Res. 2003;11(6):769–75.

    PubMed  Google Scholar 

  116. Brandt M, Harder K, Walluscheck KP, Schottler J, Rahimi A, Moller F, et al. Severe obesity does not adversely affect perioperative mortality and morbidity in coronary artery bypass surgery. Eur J Cardiothorac Surg. 2001;19(5):662–6.

    PubMed  CAS  Google Scholar 

  117. Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Obesity is not a risk factor for significant adverse outcomes after cardiac surgery. Circulation. 1996;94(9):II87–92.

    PubMed  CAS  Google Scholar 

  118. Dossett LA, Heffernan D, Lightfoot M, Collier B, Diaz JJ, Sawyer RG, et al. Obesity and pulmonary complications in critically injured adults. Chest. 2008;134(5):974–80.

    PubMed  Google Scholar 

  119. Gardner S, Jaing C, McLoughlin K, Slezak T. A microbial detection array (MDA) for viral and bacterial detection. BMC Genomics. 2010;11(1):668.

    PubMed  Google Scholar 

  120. Ahima RS. Digging deeper into obesity. J Clin Invest. 2011;121(6):2076–9.

    PubMed  CAS  Google Scholar 

  121. Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care. 2003;26(2):510–3.

    PubMed  Google Scholar 

  122. Valdez R, Narayan KM, Geiss LS, Engelgau MM. Impact of diabetes mellitus on mortality associated with pneumonia and influenza among non-Hispanic black and white US adults. Am J Public Health. 1999;89(11):1715–21.

    PubMed  CAS  Google Scholar 

  123. Yende S, van der Poll T, Lee M, Huang DT, Newman AB, Kong L, et al. The influence of pre-existing diabetes mellitus on the host immune response and outcome of pneumonia: analysis of two multicentre cohort studies. Thorax. 2010;65(10):870–7.

    PubMed  Google Scholar 

  124. Koenig SM. Pulmonary complications of obesity. Am J Med Sci. 2001;321(4):249–79.

    PubMed  CAS  Google Scholar 

  125. Marik P, Varon J. The obese patient in the ICU. Chest. 1998;113:492–8.

    PubMed  CAS  Google Scholar 

  126. Morgan OW, Bramley A, Fowlkes A, Freedman DS, Taylor TH, Gargiullo P, et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease. PLoS One. 2010;5(3):e9694.

    PubMed  Google Scholar 

  127. Karlsson EA, Beck MA. The burden of obesity on infectious disease. Exp Biol Med (Maywood). 2010;235(12):1412–24.

    CAS  Google Scholar 

  128. Finlay D, Cantrell DA. Metabolism, migration and memory in cytotoxic T cells. Nat Rev Immunol. 2011;11(2):109–17.

    PubMed  CAS  Google Scholar 

  129. Hsu A, Aronoff DM, Phipps J, Goel D, Mancuso P. Leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Clin Exp Immunol. 2007;150(2):332–9.

    PubMed  CAS  Google Scholar 

  130. Ordway D, Henao-Tamayo M, Smith E, Shanley C, Harton M, Troudt J, et al. Animal model of Mycobacterium abscessus lung infection. J Leukoc Biol. 2008;83(6):1502–11.

    PubMed  CAS  Google Scholar 

  131. Wieland CW, Florquin S, Chan ED, Leemans JC, Weijer S, Verbon A, et al. Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice. Int Immunol. 2005;17(11):1399–408.

    PubMed  CAS  Google Scholar 

  132. Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martin-Romero C, Perez-Perez A, Gonzalez-Yanes C, et al. Role of leptin in the activation of immune cells. Mediators Inflamm. 2010;2010:568343.

    PubMed  Google Scholar 

  133. Bailie MB, Standiford TJ, Laichalk LL, Coffey MJ, Strieter RM, Peters-Golden M. Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities. J Immunol. 1996;157:5221–4.

    PubMed  CAS  Google Scholar 

  134. Mancuso P, Lewis C, Serezani CH, Goel D, Peters-Golden M. Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia. Infect Immun. 2010;78(5):2264–71.

    PubMed  CAS  Google Scholar 

  135. Ikejima S, Sasaki S, Sashinami H, Mori F, Ogawa Y, Nakamura T, et al. Impairment of host resistance to Listeria monocytogenes infection in liver of db/db and ob/ob mice. Diabetes. 2005;54(1):182–9.

    PubMed  CAS  Google Scholar 

  136. Conge GA, Gouache P, Joyeux Y, Goichot J, Fournier JM. Influence of different types of experimental obesity on resistance of the mouse to infection by Salmonella typhimurium and Klebsiella pneumoniae. Ann Nutr Metab. 1988;32(3):113–20.

    PubMed  CAS  Google Scholar 

  137. Tschop J, Nogueiras R, Haas-Lockie S, Kasten KR, Castaneda TR, Huber N, et al. CNS leptin action modulates immune response and survival in sepsis. J Neurosci. 2010;30(17):6036–47.

    PubMed  Google Scholar 

  138. Park S, Rich J, Hanses F, Lee JC. Defects in innate immunity predispose C57BL/6 J- Leprdb/Leprdb mice to infection by Staphylococcus aureus. Infect Immun. 2009;77(3):1008–14.

    PubMed  CAS  Google Scholar 

  139. Wehrens A, Aebischer T, Meyer TF, Walduck AK. Leptin receptor signaling is required for vaccine-induced protection against Helicobacter pylori. Helicobacter. 2008;13(2):94–102.

    PubMed  CAS  Google Scholar 

  140. D’Andrea BJ, Wilson GL, Craighead JE. Effect of genetic obesity in mice on the induction of diabetes by encephalomyocarditis virus. Diabetes. 1981;30(5):451–4.

    PubMed  Google Scholar 

  141. Webb SR, Loria RM, Madge GE, Kibrick S. Susceptibility of mice to group B coxsackie virus is influenced by the diabetic gene. J Exp Med. 1976;143(5):1239–48.

    PubMed  CAS  Google Scholar 

  142. Plotkin BJ, Paulson D, Chelich A, Jurak D, Cole J, Kasimos J, et al. Immune responsiveness in a rat model for type II diabetes (Zucker rat, fa/fa): susceptibility to Candida albicans infection and leucocyte function. J Med Microbiol. 1996;44:277–83.

    PubMed  CAS  Google Scholar 

  143. Wieland CW, Stegenga ME, Florquin S, Fantuzzi G, van der Poll T. Leptin and host defense against gram-positive and gram-negative pneumonia in mice. Shock. 2006;25(4):414–9.

    PubMed  CAS  Google Scholar 

  144. Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab. 1999;84(10):3686–95.

    PubMed  CAS  Google Scholar 

  145. Reed AS, Unger EK, Olofsson LE, Piper ML, Myers Jr MG, Xu AW. Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long- term energy homeostasis. Diabetes. 2010;59(4):894–906.

    PubMed  CAS  Google Scholar 

  146. Nave H, Mueller G, Siegmund B, Jacobs R, Stroh T, Schueler U, et al. Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity. Endocrinology. 2008;149(7):3370–8.

    PubMed  CAS  Google Scholar 

  147. Papathanassoglou E, El-Haschimi K, Li XC, Matarese G, Strom T, Mantzoros C. Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. J Immunol. 2006;176(12):7745–52.

    PubMed  CAS  Google Scholar 

  148. Tsiotra PC, Pappa V, Raptis SA, Tsigos C. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin’s actions. Metabolism. 2000;49(12):1537–41.

    PubMed  CAS  Google Scholar 

  149. Farooqi IS, Bullmore E, Keogh J, Gillard J, O’Rahilly S, Fletcher PC. Leptin regulates striatal regions and human eating behavior. Science. 2007;317(5843):1355.

    PubMed  CAS  Google Scholar 

  150. Duggal P, Guo X, Haque R, Peterson KM, Ricklefs S, Mondal D, et al. A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. J Clin Invest. 2011;121(3):1191–8.

    PubMed  CAS  Google Scholar 

  151. Buettner R, Scholmerich J, Bollheimer LC. High-fat diets: modeling the metabolic disorders of human obesity in rodents[ast]. Obesity. 2007;15(4):798–808.

    PubMed  CAS  Google Scholar 

  152. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006;116(11):3015–25.

    PubMed  CAS  Google Scholar 

  153. Smith AG, Sheridan PA, Harp JB, Beck MA. Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J Nutr. 2007;137(5):1236–43.

    PubMed  CAS  Google Scholar 

  154. Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA. Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology. 2009;126(2):268–79.

    PubMed  CAS  Google Scholar 

  155. Karlsson EA, Sheridan PA, Beck MA. Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells. J Nutr. 2010;140(9):1691–7.

    PubMed  CAS  Google Scholar 

  156. Easterbrook JD, Dunfee RL, Schwartzman LM, Jagger BW, Sandouk A, Kash JC, et al. Obese mice have increased morbidity and mortality compared to non-obese mice during infection with the 2009 pandemic H1N1 influenza virus. Influenza Other Respi Viruses. 2011;5(6):418–25.

    PubMed  Google Scholar 

  157. Karlsson EA, Sheridan PA, Beck MA. Diet-induced obesity impairs the T cell memory response to influenza virus infection. J Immunol. 2010;184(6):3127–33.

    PubMed  CAS  Google Scholar 

  158. Strandberg L, Verdrengh M, Enge M, Andersson N, Amu S, Önnheim K, et al. Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis. PLoS One. 2009;4(10):e7605.

    PubMed  Google Scholar 

  159. Amar S, Zhou Q, Shaik-Dasthagirisaheb Y, Leeman S. Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge. Proc Natl Acad Sci USA. 2007;104(51):20466–71.

    PubMed  CAS  Google Scholar 

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  1. Environmental Health Sciences and Graduate Program in Immunology, 109 S. Observatory, Ann Arbor, MI, 48109, USA

    Peter Mancuso M.S., Ph.D.

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  1. , Pulmonary and Critical Care Medicine, University of Vermont College of Medicin, 89 Beaumont Ave., Burlington, 05405, Vermont, USA

    Anne E. Dixon

  2. , Clinical Development Medical Affairs, Respiratory Boehringer Ingelheim Pharmac, N/A, Ridgefield, 06877, Connecticut, USA

    Emmanuelle M. Clerisme-Beaty

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Mancuso, P. (2013). The Effects of Obesity on Immune Function and Pulmonary Host Defense. In: Dixon, A., Clerisme-Beaty, E. (eds) Obesity and Lung Disease. Respiratory Medicine, vol 19. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-053-3_3

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