Commensal Bacterial Outer Membrane Protein A Induces Interleukin-22 Production

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2024 Jun 1

PMID 38823020

Authors

Yanling Wang

Vu L Ngo

Jun Zou

Andrew T Gewirtz

Affiliations

Soon will be listed here.

Abstract

Interleukin (IL)-22 promotes host-microbiota homeostasis. We sought to identify microbiota metabolite(s) that drive intestinal IL-22 production. We observed that exposing Peyer's patch cells (PPCs), ex vivo, to fecal supernatants (FSs) recapitulates fermentable fiber- and microbiota-dependent IL-22 production, and cellular sources thereof, thus supporting the use of this model. An interrogation of FSs generated from mice fed the fermentable fiber inulin (FS-Inu) revealed that its IL-22-inducing activity is mediated by heat-labile protein. Fractionation of FS-Inu by ion-exchange chromatography, and subsequent proteomic analysis of IL-22-inducing fractions, indicates that outer membrane protein A (OmpA) might be a microbial driver of IL-22 expression. Concomitantly, recombinant OmpA from Parabacteroides goldsteinii, which is enriched by an inulin diet, induces IL-22 production and expression of the IL-22-dependent genes REG3γ and -β, in PPCs and mice. Thus, OmpA is one bacterial inducer of IL-22 expression, potentially linking diet, mucosal immune homeostasis, and gut health.

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References

Gophna U, Ideses D, Rosen R, Grundland A, Ron E . OmpA of a septicemic Escherichia coli O78--secretion and convergent evolution. Int J Med Microbiol. 2004; 294(6):373-81. DOI: 10.1016/j.ijmm.2004.08.004. View

Sakamoto M, Benno Y . Reclassification of Bacteroides distasonis, Bacteroides goldsteinii and Bacteroides merdae as Parabacteroides distasonis gen. nov., comb. nov., Parabacteroides goldsteinii comb. nov. and Parabacteroides merdae comb. nov. Int J Syst Evol Microbiol. 2006; 56(Pt 7):1599-1605. DOI: 10.1099/ijs.0.64192-0. View

Zenewicz L . IL-22: There Is a Gap in Our Knowledge. Immunohorizons. 2019; 2(6):198-207. PMC: 10518850. DOI: 10.4049/immunohorizons.1800006. View

Zindl C, Lai J, Lee Y, Maynard C, Harbour S, Ouyang W . IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. Proc Natl Acad Sci U S A. 2013; 110(31):12768-73. PMC: 3732935. DOI: 10.1073/pnas.1300318110. View

Cui Y, Zhang L, Wang X, Yi Y, Shan Y, Liu B . Roles of intestinal Parabacteroides in human health and diseases. FEMS Microbiol Lett. 2022; 369(1). DOI: 10.1093/femsle/fnac072. View

Nie D, Hu Y, Chen Z, Li M, Hou Z, Luo X . Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection. J Biomed Sci. 2020; 27(1):26. PMC: 6969976. DOI: 10.1186/s12929-020-0617-7. View

Zou J, Chassaing B, Singh V, Pellizzon M, Ricci M, Fythe M . Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health. Cell Host Microbe. 2017; 23(1):41-53.e4. PMC: 6005180. DOI: 10.1016/j.chom.2017.11.003. View

Chalifour A, Jeannin P, Gauchat J, Blaecke A, Malissard M, Nguyen T . Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood. 2004; 104(6):1778-83. DOI: 10.1182/blood-2003-08-2820. View

Davies R, Quirie M . Intra-specific diversity within Pasteurella trehalosi based on variation of capsular polysaccharide, lipopolysaccharide and outer-membrane proteins. Microbiology (Reading). 1996; 142 ( Pt 3):551-560. DOI: 10.1099/13500872-142-3-551. View

10.

Smith S, Mahon V, Lambert M, Fagan R . A molecular Swiss army knife: OmpA structure, function and expression. FEMS Microbiol Lett. 2007; 273(1):1-11. DOI: 10.1111/j.1574-6968.2007.00778.x. View

11.

Torres A, Li Y, Tutt C, Xin L, Eaves-Pyles T, Soong L . Outer membrane protein A of Escherichia coli O157:H7 stimulates dendritic cell activation. Infect Immun. 2006; 74(5):2676-85. PMC: 1459721. DOI: 10.1128/IAI.74.5.2676-2685.2006. View

12.

Yang W, Yu T, Huang X, Bilotta A, Xu L, Lu Y . Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun. 2020; 11(1):4457. PMC: 7478978. DOI: 10.1038/s41467-020-18262-6. View

13.

Koebnik R, Locher K, Van Gelder P . Structure and function of bacterial outer membrane proteins: barrels in a nutshell. Mol Microbiol. 2000; 37(2):239-53. DOI: 10.1046/j.1365-2958.2000.01983.x. View

14.

Klotskova H, Kidess E, Nadal A, Brugman S . The role of interleukin-22 in mammalian intestinal homeostasis: Friend and foe. Immun Inflamm Dis. 2024; 12(2):e1144. PMC: 10870696. DOI: 10.1002/iid3.1144. View

15.

Chassaing B, Gewirtz A . Mice harboring pathobiont-free microbiota do not develop intestinal inflammation that normally results from an innate immune deficiency. PLoS One. 2018; 13(4):e0195310. PMC: 5884553. DOI: 10.1371/journal.pone.0195310. View

16.

Zou J, Ngo V, Wang Y, Wang Y, Gewirtz A . Maternal fiber deprivation alters microbiota in offspring, resulting in low-grade inflammation and predisposition to obesity. Cell Host Microbe. 2022; 31(1):45-57.e7. PMC: 9850817. DOI: 10.1016/j.chom.2022.10.014. View

17.

Macia L, Nanan R, Hosseini-Beheshti E, Grau G . Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development. Int J Mol Sci. 2019; 21(1). PMC: 6982009. DOI: 10.3390/ijms21010107. View

18.

Brand M, Wannemuehler M, Phillips G, Proctor A, Overstreet A, Jergens A . The Altered Schaedler Flora: Continued Applications of a Defined Murine Microbial Community. ILAR J. 2015; 56(2):169-78. PMC: 4554250. DOI: 10.1093/ilar/ilv012. View

19.

Confer A, Ayalew S . The OmpA family of proteins: roles in bacterial pathogenesis and immunity. Vet Microbiol. 2012; 163(3-4):207-22. DOI: 10.1016/j.vetmic.2012.08.019. View

20.

Kinnebrew M, Buffie C, Diehl G, Zenewicz L, Leiner I, Hohl T . Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity. 2012; 36(2):276-87. PMC: 3288454. DOI: 10.1016/j.immuni.2011.12.011. View