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Clinical and Molecular Allergy
Published in: Clinical and Molecular Allergy 1/2010

Open Access 01-12-2010 | Research

IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring

Authors: Adam P Matson, Roger S Thrall, Ektor Rafti, Elizabeth G Lingenheld, Lynn Puddington

Published in: Clinical and Molecular Allergy | Issue 1/2010

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Abstract

Background

The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors.

Objective

The aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy.

Methods

Allergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn+/- or FcRn-/- progeny born to FcRn+/- females that were mated to C57BL/6J-FcRn-/- male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization.

Results

Levels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG1 to breastfed FcRn-/- offspring was at levels 103-104 lower than observed in FcRn+/- or FcRn+/+ mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology.

Conclusions

FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.
Appendix
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Literature
1.
Newburg DS: Bioactive components of human milk: evolution, efficiency, and protection. Adv Exp Med Biol. 2001, 501: 3-10.CrossRefPubMed
2.
Labbok MH, Clark D, Goldman AS: Breastfeeding: maintaining an irreplaceable immunological resource. Nat Rev Immunol. 2004, 4: 565-572. 10.1038/nri1393CrossRefPubMed
3.
Gartner LM, Morton J, Lawrence RA, Naylor AJ, O'Hare D, Schanler RJ: Breastfeeding and the use of human milk. Pediatrics. 2005, 115: 496-506. 10.1542/peds.2004-2491CrossRefPubMed
4.
Ip S, Chung M, Raman G, Chew P, Magula N, Devine D: Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess. 2007, 1-186.
5.
Ehrlich P: "Collected Papers, "Vol.II. Z Hygiene. 1892, 12: 31-44.
6.
Brambell FW, Halliday R, Brierley J, Hemmings WA: Transference of passive immunity from mother to young. Lancet. 1954, 266: 964-965.CrossRefPubMed
7.
Zinkernagel RM: Maternal antibodies, childhood infections, and autoimmune diseases. N Engl J Med. 2001, 345: 1331-1335. 10.1056/NEJMra012493CrossRefPubMed
8.
Simister NE, Story CM, Chen HL, Hunt JS: An IgG-transporting Fc receptor expressed in the syncytiotrophoblast of human placenta. Eur J Immunol. 1996, 26: 1527-1531. 10.1002/eji.1830260718CrossRefPubMed
9.
Jones EA, Waldmann TA: The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J Clin Invest. 1972, 51: 2916-2927. 10.1172/JCI107116PubMedCentralCrossRefPubMed
10.
11.
Israel EJ, Taylor S, Wu Z, Mizoguchi E, Blumberg RS, Bhan A: Expression of the neonatal Fc receptor, FcRn, on human intestinal epithelial cells. Immunology. 1997, 92: 69-74. 10.1046/j.1365-2567.1997.00326.xPubMedCentralCrossRefPubMed
12.
Simister NE, Mostov KE: An Fc receptor structurally related to MHC class I antigens. Nature. 1989, 337: 184-187. 10.1038/337184a0CrossRefPubMed
13.
Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N: The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol. 2003, 170: 3528-3533.CrossRefPubMed
14.
He W, Ladinsky MS, Huey-Tubman KE, Jensen GJ, McIntosh JR, Bjorkman PJ: FcRn-mediated antibody transport across epithelial cells revealed by electron tomography. Nature. 2008, 455: 542-546. 10.1038/nature07255PubMedCentralCrossRefPubMed
15.
Ghetie V, Hubbard JG, Kim JK, Tsen MF, Lee Y, Ward ES: Abnormally short serum half-lives of IgG in beta 2-microglobulin-deficient mice. Eur J Immunol. 1996, 26: 690-696. 10.1002/eji.1830260327CrossRefPubMed
16.
Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC: The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med. 2003, 197: 315-322. 10.1084/jem.20021829PubMedCentralCrossRefPubMed
17.
Israel EJ, Patel VK, Taylor SF, Marshak-Rothstein A, Simister NE: Requirement for a beta 2-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice. J Immunol. 1995, 154: 6246-6251.PubMed
18.
Akilesh S, Christianson GJ, Roopenian DC, Shaw AS: Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism. J Immunol. 2007, 179: 4580-4588.CrossRefPubMed
19.
Montoyo HP, Vaccaro C, Hafner M, Ober RJ, Mueller W, Ward ES: Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proc Natl Acad Sci USA. 2009, 106: 2788-2793. 10.1073/pnas.0810796106PubMedCentralCrossRefPubMed
20.
Ghetie V, Ward ES: Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annu Rev Immunol. 2000, 18: 739-766. 10.1146/annurev.immunol.18.1.739CrossRefPubMed
21.
Yoshida M, Kobayashi K, Kuo TT, Bry L, Glickman JN, Claypool SM: Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J Clin Invest. 2006, 116: 2142-2151. 10.1172/JCI27821PubMedCentralCrossRefPubMed
22.
Kobayashi K, Qiao SW, Yoshida M, Baker K, Lencer WI, Blumberg RS: An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice. Gastroenterology. 2009, 137: 1746-1756. 10.1053/j.gastro.2009.07.059PubMedCentralCrossRefPubMed
23.
24.
Victor JR Jr, Fusaro AE, Duarte AJ, Sato MN: Preconception maternal immunization to dust mite inhibits the type I hypersensitivity response of offspring. J Allergy Clin Immunol. 2003, 111: 269-277. 10.1067/mai.2003.39CrossRefPubMed
25.
Uthoff H, Spenner A, Reckelkamm W, Ahrens B, Wolk G, Hackler R: Critical role of preconceptional immunization for protective and nonpathological specific immunity in murine neonates. J Immunol. 2003, 171: 3485-3492.CrossRefPubMed
26.
Oshiba A, Hamelmann E, Takeda K, Bradley KL, Loader JE, Larsen GL: Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice. J Clin Invest. 1996, 97: 1398-1408. 10.1172/JCI118560PubMedCentralCrossRefPubMed
27.
von Garnier C, Wikstrom ME, Zosky G, Turner DJ, Sly PD, Smith M: Allergic airways disease develops after an increase in allergen capture and processing in the airway mucosa. J Immunol. 2007, 179: 5748-5759.CrossRefPubMed
28.
Matson AP, Thrall RS, Rafti E, Puddington L: Breastmilk from allergic mothers can protect offspring from allergic airway inflammation. Breastfeed Med. 2009, 4: 167-174. 10.1089/bfm.2008.0130PubMedCentralCrossRefPubMed
29.
Matson AP, Zhu L, Lingenheld EG, Schramm CM, Clark RB, Selander DM: Maternal transmission of resistance to development of allergic airway disease. J Immunol. 2007, 179: 1282-1291.PubMedCentralCrossRefPubMed
30.
Wu CA, Puddington L, Whiteley HE, Yiamouyiannis CA, Schramm CM, Mohammadu F: Murine cytomegalovirus infection alters Th1/Th2 cytokine expression, decreases airway eosinophilia, and enhances mucus production in allergic airway disease. J Immunol. 2001, 167: 2798-2807.CrossRefPubMed
31.
Lohning M, Stroehmann A, Coyle AJ, Grogan JL, Lin S, Gutierrez-Ramos JC: T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci USA. 1998, 95: 6930-6935. 10.1073/pnas.95.12.6930PubMedCentralCrossRefPubMed
32.
Masopust D, Vezys V, Marzo AL, Lefrançois L: Preferential localization of effector memory cells in nonlymphoid tissue. Science. 2001, 291: 2413-2417. 10.1126/science.1058867CrossRefPubMed
33.
Seymour BWP, Gershwin LJ, Coffman RL: Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-γ/δ+ T cells or interferon (IFN)-γ in a murine model of allergen sensitization. J Exp Med. 1998, 187: 721-731. 10.1084/jem.187.5.721PubMedCentralCrossRefPubMed
34.
Roopenian DC, Christianson GJ, Sproule TJ: Human FcRn transgenic mice for pharmacokinetic evaluation of therapeutic antibodies. Methods Mol Biol. 2010, 602: 93-104. full_textCrossRefPubMed
35.
Schramm CM, Puddington L, Yiamouyiannis CA, Lingenheld EG, Whiteley HE, Wolyniec WW: Proinflammatory roles of TCRγδ and TCRαβ lymphocytes in a murine model of asthma. Am J Respir Cell Mol Biol. 2000, 22: 218-225.CrossRefPubMed
36.
Nakata K, Kobayashi K, Ishikawa Y, Yamamoto M, Funada Y, Kotani Y: The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner. Biochem Biophys Res Commun. 2010, 395: 238-243. 10.1016/j.bbrc.2010.03.170PubMedCentralCrossRefPubMed
37.
Friedman NJ, Zeiger RS: The role of breast-feeding in the development of allergies and asthma. J Allergy Clin Immunol. 2005, 115: 1238-1248. 10.1016/j.jaci.2005.01.069CrossRefPubMed
38.
Polte T, Hennig C, Hansen G: Allergy prevention starts before conception: maternofetal transfer of tolerance protects against the development of asthma. J Allergy Clin Immunol. 2008, 122: 1022-1030. 10.1016/j.jaci.2008.09.014CrossRefPubMed
39.
Fusaro AE, Maciel M, Victor JR, Oliveira CR, Duarte AJ, Sato MN: Influence of maternal murine immunization with Dermatophagoides pteronyssinus extract on the type I hypersensitivity response in offspring. Int Arch Allergy Immunol. 2002, 127: 208-216. 10.1159/000053865CrossRefPubMed
40.
Jarrett E, Hall E: Selective suppression of IgE antibody responsiveness by maternal influence. Nature. 1979, 280: 145-147. 10.1038/280145a0CrossRefPubMed
41.
Victor JR, Muniz BP, Fusaro AE, de Brito CA, Taniguchi EF, Duarte AJ: Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells. BMC Immunol. 2010, 11: 11. 10.1186/1471-2172-11-11PubMedCentralCrossRefPubMed
42.
Leme AS, Hubeau C, Xiang Y, Goldman A, Hamada K, Suzaki Y: Role of breast milk in a mouse model of maternal transmission of asthma susceptibility. J Immunol. 2006, 176: 762-769.CrossRefPubMed
43.
Siegrist CA: Neonatal and early life vaccinology. Vaccine. 2001, 19: 3331-3346. 10.1016/S0264-410X(01)00028-7CrossRefPubMed
44.
Albrecht P, Ennis FA, Saltzman EJ, Krugman S: Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure. J Pediatr. 1977, 91: 715-718. 10.1016/S0022-3476(77)81021-4CrossRefPubMed
45.
Lambert PH, Liu M, Siegrist CA: Can successful vaccines teach us how to induce efficient protective immune responses?. Nat Med. 2005, 11: S54-S62. 10.1038/nm1216CrossRefPubMed
46.
Mosconi E, Rekima A, Seitz-Polski B, Kanda A, Fleury S, Tissandie E: Breast milk immune complexes are potent inducers of oral tolerance in neonates and prevent asthma development. Mucosal Immunol. 2010, 3: doi:10.1038/mi.2010.23
47.
Lopez-Exposito I, Song Y, Jarvinen KM, Srivastava K, Li XM: Maternal peanut exposure during pregnancy and lactation reduces peanut allergy risk in offspring. J Allergy Clin Immunol. 2009, 124: 1039-1046. 10.1016/j.jaci.2009.08.024PubMedCentralCrossRefPubMed
48.
Tincani A, Rebaioli CB, Frassi M, Taglietti M, Gorla R, Cavazzana I: Pregnancy and autoimmunity: maternal treatment and maternal disease influence on pregnancy outcome. Autoimmun Rev. 2005, 4: 423-428. 10.1016/j.autrev.2005.03.001CrossRefPubMed
49.
Kaneko Y, Nimmerjahn F, Ravetch JV: Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science. 2006, 313: 670-673. 10.1126/science.1129594CrossRefPubMed
50.
Nimmerjahn F, Ravetch JV: Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science. 2005, 310: 1510-1512. 10.1126/science.1118948CrossRefPubMed
51.
Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Stanworth D: Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature. 1985, 316: 452-457. 10.1038/316452a0CrossRefPubMed
52.
Holland M, Yagi H, Takahashi N, Kato K, Savage CO, Goodall DM: Differential glycosylation of polyclonal IgG, IgG-Fc and IgG-Fab isolated from the sera of patients with ANCA-associated systemic vasculitis. Biochim Biophys Acta. 2006, 1760: 669-677.CrossRefPubMed
Metadata
Title
IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring
Authors
Adam P Matson
Roger S Thrall
Ektor Rafti
Elizabeth G Lingenheld
Lynn Puddington
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Clinical and Molecular Allergy / Issue 1/2010
Electronic ISSN: 1476-7961
DOI
https://doi.org/10.1186/1476-7961-8-9

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