Published in:

Open Access 08-06-2024 | Pseudomonas Aeruginosa | Original Research Paper

Saccharomyces cerevisiae β-glucan improves the response of trained macrophages to severe P. aeruginosa infections

Authors: Marta Ciszek-Lenda, Bernadeta Nowak, Grzegorz Majka, Maciej Suski, Maria Walczewska, Angelika Fedor, Edyta Golińska, Sabina Górska, Andrzej Gamian, Rafał Olszanecki, Magdalena Strus, Janusz Marcinkiewicz

Published in: Inflammation Research | Issue 8/2024

Abstract

Objective P. Aeruginosa

(PA), the major pathogen of lung cystic fibrosis (CF), polarizes macrophages into hyperinflammatory tissue damaging phenotype. The main aim of this study was to verify whether training of macrophages with β-glucan might improve their response to P. aeruginosa infections.

Methods

To perform this task C57BL/6 mice sensitive to infections with P. aeruginosa were used. Peritoneal macrophages were trained with Saccharomyces cerevisiae β-glucan and exposed to PA57, the strong biofilm-forming bacterial strain isolated from the patient with severe lung CF. The release of cytokines and the expression of macrophage phenotypic markers were measured. A quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. The effect of in vivo β-glucan-trained macrophages in the air pouch model of PA57 infection was investigated. In all experiments the effect of trained and naïve macrophages was compared.

Results

Trained macrophages acquired a specific phenotype with mixed pro-inflammatory and pro-resolution characteristics, however they retained anti-bacterial properties. Most importantly, transfer of trained macrophages into infected air pouches markedly ameliorated the course of infection. PA57 bacterial growth and formation of biofilm were significantly suppressed. The level of serum amyloid A (SAA), a systemic inflammation biomarker, was reduced.

Conclusions

Training of murine macrophages with S. cerevisiae β-glucan improved macrophage defense properties along with inhibition of secretion of some detrimental inflammatory agents. We suggest that training of macrophages with such β-glucans might be a new therapeutic strategy in P. aeruginosa biofilm infections, including CF, to promote eradication of pathogens and resolution of inflammation.

Available only for authorised users

Davies JC. Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respirat Rev. 2002;3(2):128–34. https://doi.org/10.1016/S1526-0550(02)00003-3.CrossRef

Ulrich M, Worlitzsch D, Viglio S, Siegmann N, Iadarola P, Shute JK, et al. Alveolar inflammation in cystic fibrosis. J Cyst Fibros. 2010;9(3):217–27. https://doi.org/10.1016/j.jcf.2010.03.001.CrossRefPubMedPubMedCentral

Allard B, Panariti A, Martin JG. Alveolar macrophages in the resolution of inflammation, tissue repair, and tolerance to infection. 2018;9. https://doi.org/10.3389/fimmu.2018.01777.

Ciszek-Lenda M, Strus M, Walczewska M, Majka G, Machul-Żwirbla A, Mikołajczyk D, et al. Pseudomonas aeruginosa biofilm is a potent inducer of phagocyte hyperinflammation. Inflamm Res. 2019;68(5):397–413. https://doi.org/10.1007/s00011-019-01227-x.CrossRefPubMedPubMedCentral

Bruscia EM, Bonfield TL. Cystic fibrosis lung immunity: the role of the macrophage. J Innate Immun. 2016;8(6):550–63. https://doi.org/10.1159/000446825.CrossRefPubMedPubMedCentral

Bekkering S, Blok BA, Joosten LAB, Riksen NP, Crevel Rv, Netea MG. Vitro Experimental Model of trained Innate. Immun Hum Prim Monocytes. 2016;23(12):926–33. https://doi.org/10.1128/CVI.00349-16.CrossRef

van der Meer JWM, Joosten LAB, Riksen N, Netea MG. Trained immunity: a smart way to enhance innate immune defence. Mol Immun. 2015;68(1):40–4. https://doi.org/10.1016/j.molimm.2015.06.019.CrossRef

Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012;12(2):223–32. https://doi.org/10.1016/j.chom.2012.06.006.CrossRefPubMed

Akpan A, Morgan R. Oral candidiasis. Postgrad Med J. 2002;78(922):455–9. https://doi.org/10.1136/pmj.78.922. .455%J Postgrad Med J.CrossRefPubMedPubMedCentral

10.

Xu X, Yasuda M, Mizuno M, Ashida H. β-Glucan from Saccharomyces cerevisiae reduces lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. Biochim Biophys Acta. 2012;1820(10):1656–63. https://doi.org/10.1016/j.bbagen.2012.06.015.CrossRefPubMed

11.

Fakruddin M, Hossain MN, Ahmed MM. Antimicrobial and antioxidant activities of Saccharomyces cerevisiae IFST062013, a potential probiotic. BMC Complement Alternat Med. 2017;17(1):64. https://doi.org/10.1186/s12906-017-1591-9.CrossRef

12.

Sapru K, Stotland PK, Stevenson MM. Quantitative and qualitative differences in bronchoalveolar inflammatory cells in Pseudomonas aeruginosa-resistant and -susceptible mice. Clin Exp Immun. 2001;115(1):103–9. https://doi.org/10.1046/j.1365-2249.1999.00762.x.CrossRef

13.

Majka G, Mazurek H, Strus M, Ciszek-Lenda M, Szatanek R, Pac A, et al. Chronic bacterial pulmonary infections in advanced cystic fibrosis differently affect the level of sputum neutrophil elastase, IL-8 and IL-6. Clin Exp Immun. 2021;205(3):391–405. https://doi.org/10.1111/cei.13624.CrossRefPubMedPubMedCentral

14.

Leonhardt J, Große S, Marx C, Siwczak F, Stengel S, Bruns T et al. Candida albicans β-Glucan differentiates human monocytes into a specific subset of macrophages. 2018;9. https://doi.org/10.3389/fimmu.2018.02818.

15.

McCarson KE, Fehrenbacher JC. Models of Inflammation: Carrageenan- or Complete Freund’s Adjuvant (CFA)–Induced Edema and Hypersensitivity in the Rat. 2021;1(7):e202. https://doi.org/10.1002/cpz1.202.

16.

Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immun. 1988;141(7):2407–12. https://doi.org/10.4049/jimmunol.141.7.2407.CrossRefPubMed

17.

Ciszek-Lenda M, Majka G, Suski M, Walczewska M, Górska S, Golińska E, et al. Biofilm-forming strains of P. Aeruginosa and S. Aureus isolated from cystic fibrosis patients differently affect inflammatory phenotype of macrophages. Inflamm Res. 2023;72(6):1275–89. https://doi.org/10.1007/s00011-023-01743-x.CrossRefPubMedPubMedCentral

18.

Wiśniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat Methods. 2009;6(5):359–62. https://doi.org/10.1038/nmeth.1322.CrossRefPubMed

19.

Wiśniewski JR, Gaugaz FZ. Fast and sensitive total protein and peptide assays for proteomic analysis. Anal Chem. 2015;87(8):4110–6. https://doi.org/10.1021/ac504689z.CrossRefPubMed

20.

Bruderer R, Bernhardt OM, Gandhi T, Miladinović SM, Cheng L-Y, Messner S, et al. Extending the limits of quantitative proteome profiling with Data-Independent Acquisition and application to acetaminophen-treated three-Dimensional Liver microtissues. Mol Cell Proteom. 2015;14(5):1400–10. https://doi.org/10.1074/mcp.M114.044305.CrossRef

21.

Storey JD. A direct approach to false discovery rates. J Royal Stat Society: Ser B (Statistical Methodology). 2002;64(3):479–98. https://doi.org/10.1111/1467-9868.00346.CrossRef

22.

Vizcaíno JA, Deutsch EW, Wang R, Csordas A, Reisinger F, Ríos D, et al. ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat Biotechnol. 2014;32(3):223–6. https://doi.org/10.1038/nbt.2839.CrossRefPubMedPubMedCentral

23.

Peruń A, Biedroń R, Konopiński MK, Białecka A, Marcinkiewicz J, Józefowski S. Phagocytosis of live versus killed or fluorescently labeled bacteria by macrophages differ in both magnitude and receptor specificity. 2017;95(5):424–35. https://doi.org/10.1038/icb.2016.112.

24.

Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020;877:173090. https://doi.org/10.1016/j.ejphar.2020.173090.CrossRefPubMed

25.

Simonin-Le Jeune K, Le Jeune A, Jouneau S, Belleguic C, Roux P-F, Jaguin M, et al. Impaired functions of macrophage from cystic fibrosis patients: CD11b, TLR-5 decrease and sCD14, Inflammtory cytokines increase. PLoS ONE. 2013;8(9):e75667. https://doi.org/10.1371/journal.pone.0075667.CrossRefPubMedPubMedCentral

26.

Pernet E, Prevel R, Divangahi M. Training can’t always lead to Olympic macrophages. J Clin Invest. 2022;132(7). https://doi.org/10.1172/jci158468.

27.

Hashimoto T, Ohno N, Adachi Y, Yadomae T. Enhanced production of inducible nitric oxide synthase by β-glucans in mice. FEMS Immunol Med Microbiol. 1997;19(2):131–5. https://doi.org/10.1111/j.1574-695X.1997.tb01082.x.CrossRefPubMed

28.

Municio C, Alvarez Y, Montero O, Hugo E, Rodríguez M, Domingo E, et al. The response of human macrophages to β-Glucans depends on the inflammatory milieu. PLoS ONE. 2013;8(4):e62016. https://doi.org/10.1371/journal.pone.0062016.CrossRefPubMedPubMedCentral

29.

Rizzetto L, Ifrim DC, Moretti S, et al. Fungal chitin induces trained immunity in human monocytes during cross-talk of the host with Saccharomyces cerevisiae. J Biol Chem. 2016;291(15):7961–72. https://doi.org/10.1074/jbc.M115.699645.CrossRefPubMedPubMedCentral

30.

Vuscan P, Kischkel B, Joosten LAB, Netea MG. Trained immunity: General and emerging concepts. Immunol Rev. 2024. https://doi.org/10.1111/imr.13326.CrossRefPubMed

31.

Shea-Donohue T, Zhao A, Antalis TM. SerpinB2 mediated regulation of macrophage function during enteric infection. Gut Microbes. 2014;5(2):254–8. https://doi.org/10.4161/gmic.28093.CrossRefPubMedPubMedCentral

32.

Vandooren J, Goeminne P, Boon L, Ugarte-Berzal E, Rybakin V, Proost P et al. Neutrophils and activated macrophages Control Mucosal immunity by Proteolytic Cleavage of Antileukoproteinase. 2018;9. https://doi.org/10.3389/fimmu.2018.01154.

33.

Holley AK, Bakthavatchalu V, Velez-Roman JM. St. Clair DK. Manganese Superoxide Dismutase: Guardian Powerhouse. 2011;12(10):7114–62.

34.

Gaggar A, Hector A, Bratcher PE, Mall MA, Griese M, Hartl D. The role of matrix metalloproteinases in cystic fibrosis lung disease. 2011;38(3):721–7. https://doi.org/10.1183/09031936.00173210.

35.

De Groote MA, Fang FC. NO inhibitions: Antimicrobial properties of nitric oxide. Clin Infect Dis. 1995;21(Supplement2):S162–5. https://doi.org/10.1093/clinids/21.Supplement_2.S162.CrossRefPubMed

36.

Fischer A, Rausell A. Primary immunodeficiencies suggest redundancy within the human immune system. 2016;1(6):eaah5861. doi: https://doi.org/10.1126/sciimmunol.aah5861.

37.

Shah C, Hari-Dass R, Raynes JG. Serum amyloid A is an innate immune opsonin for Gram-negative bacteria. Blood. 2006;108(5):1751–7. https://doi.org/10.1182/blood-2005-11-011932.CrossRefPubMed

38.

Chakraborty S, Kaur S, Guha S, Batra SK. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta (BBA) –. Rev Cancer. 2012;1826(1):129–69. https://doi.org/10.1016/j.bbcan.2012.03.008.CrossRef

39.

Hirano M, Davis RS, Fine WD, Nakamura S, Shimizu K, Yagi H, et al. IgEb immune complexes activate macrophages through FcgammaRIV binding. Nat Immun. 2007;8(7):762–71. https://doi.org/10.1038/ni1477.CrossRef

40.

Wang L, Wu D, Robinson CV, Wu H, Fu TM. Structures of a complete human V-ATPase reveal mechanisms of its Assembly. Mol Cell. 2020;80(3):501–e113. https://doi.org/10.1016/j.molcel.2020.09.029.CrossRefPubMedPubMedCentral

41.

Doyen V, Rubio M, Braun D, Nakajima T, Abe J, Saito H, et al. Thrombospondin 1 is an autocrine negative regulator of human dendritic cell activation. J Exp Med. 2003;198(8):1277–83. https://doi.org/10.1084/jem.20030705.CrossRefPubMedPubMedCentral

42.

Xu X, Yasuda M, Mizuno M, Ashida H. beta glucan from Saccharomyces cerevisiae reduces lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages. Biochim Biophys Acta. 2012;1820(10):1656–63. https://doi.org/10.1016/j.bbagen.2012.06.015.CrossRefPubMed

43.

Vodovotz Y, Bogdan C, Paik Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta. J Exp Med., Yang X, Li S, Zhao Y, Li S, Zhao T, Tai Y et al. GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice. 2019;8(12):1596.

44.

Tsuge K, Inazumi T, Shimamoto A, Sugimoto Y. Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases. Int Immun. 2019;31(9):597–606. https://doi.org/10.1093/intimm/dxz021 International Immunology.

45.

Yamauchi K, Kasuya Y, Kuroda F, Tanaka K, Tsuyusaki J, Ishizaki S, et al. Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin. Respir Res. 2011;12(1):131. https://doi.org/10.1186/1465-9921-12-131.CrossRefPubMedPubMedCentral

Title: Saccharomyces cerevisiae β-glucan improves the response of trained macrophages to severe P. aeruginosa infections
Authors: Marta Ciszek-Lenda
Bernadeta Nowak
Grzegorz Majka
Maciej Suski
Maria Walczewska
Angelika Fedor
Edyta Golińska
Sabina Górska
Andrzej Gamian
Rafał Olszanecki
Magdalena Strus
Janusz Marcinkiewicz
Publication date: 08-06-2024
Publisher: Springer International Publishing
Keywords: Pseudomonas Aeruginosa
Cystic Fibrosis
Cystic Fibrosis
Published in: Inflammation Research / Issue 8/2024
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-024-01898-1

Comprehensive analysis of single cell and bulk RNA sequencing reveals the heterogeneity of melanoma tumor microenvironment and predicts the response of immunotherapy

Checkpoint Inhibitors
Original Research Paper

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury

Acute Kidney Injury
Original Research Paper

Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease

Open Access
Inflammatory Bowel Disease
Original Research Paper

Anti-rheumatic property and physiological safety of KMU-11342 in in vitro and in vivo models

Open Access
Rheumatoid Arthritis
Original Research Paper

A synthetic bioactive peptide of the C-terminal fragment of adhesion protein Fibulin7 attenuates the inflammatory functions of innate immune cells in LPS-induced systemic inflammation

Septicemia
Original Research Paper

NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype

Open Access
Original Research Paper

Keynote series | Spotlight on managing health in obesity

Obesity
Video Series

Obesity is a major contributor to cardiorenal metabolic disease, but its impact extends throughout the body. Understand how obesity can affect other organ systems and impact treatment, and whether weight-loss measures improve outcomes.

Prof. Eva L. Feldman

Prof. Jonette Keri

Developed by: Springer Medicine

Watch now

Women’s health knowledge hub

Menopause
Clinical Collection

Elevate your patient care with our comprehensive, evidence-based medical education on women's health. Designed to help you provide exceptional care for your female patients at every stage of life, we provide expert insights into topics such as reproductive health, menopause, breast cancer and sex-specific health risks and precision medicine.

Live
Webinar | 27-05-2025 | 18:00 (CEST)

Systemic lupus erythematosus is a severe autoimmune disease that can cause damage to almost every system of the body. Join this session to learn more about novel biomarkers for diagnosis and monitoring and familiarise yourself with current and emerging targeted therapies.

Join us live: Tuesday 27th May, 18:00-19:15 (CEST)

Prof. Edward Vital

Prof. Ronald F. van Vollenhoven

Developed by: Springer Medicine

Keynote series | Spotlight on managing health in obesity

Springer Medicine

Saccharomyces cerevisiae β-glucan improves the response of trained macrophages to severe P. aeruginosa infections

Abstract

Objective P. Aeruginosa

Methods

Results

Conclusions

Other articles of this Issue 8/2024

Comprehensive analysis of single cell and bulk RNA sequencing reveals the heterogeneity of melanoma tumor microenvironment and predicts the response of immunotherapy

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury

Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease

Anti-rheumatic property and physiological safety of KMU-11342 in in vitro and in vivo models

A synthetic bioactive peptide of the C-terminal fragment of adhesion protein Fibulin7 attenuates the inflammatory functions of innate immune cells in LPS-induced systemic inflammation

NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype

Keynote series | Spotlight on managing health in obesity

Women’s health knowledge hub

Keynote webinar | Spotlight on advances in lupus

Springer Medicine

Abstract

Objective P. Aeruginosa

Methods

Results

Conclusions

Please log in to get access to this content