The Cytokine IL-22 Promotes Pathogen Colonization by Suppressing Related Commensal Bacteria

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2014 Feb 11

PMID 24508234

Citations 170

Authors

Judith Behnsen

Stefan Jellbauer

Christina P Wong

Robert A Edwards

Michael D George

Wenjun Ouyang

Manuela Raffatellu

Affiliations

Soon will be listed here.

Abstract

Interleukin-22 (IL-22) is highly induced in response to infections with a variety of pathogens, and its main functions are considered to be tissue repair and host defense at mucosal surfaces. Here we showed that IL-22 has a unique role during infection in that its expression suppressed the intestinal microbiota and enhanced the colonization of a pathogen. IL-22 induced the expression of antimicrobial proteins, including lipocalin-2 and calprotectin, which sequester essential metal ions from microbes. Because Salmonella enterica ser. Typhimurium can overcome metal ion starvation mediated by lipocalin-2 and calprotectin via alternative pathways, IL-22 boosted its colonization of the inflamed intestine by suppressing commensal Enterobacteriaceae, which are susceptible to the antimicrobial proteins. Thus, IL-22 tipped the balance between pathogenic and commensal bacteria in favor of a pathogen. Taken together, IL-22 induction can be exploited by pathogens to suppress the growth of their closest competitors, thereby enhancing pathogen colonization of mucosal surfaces.

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References

Hantke K, Nicholson G, Rabsch W, Winkelmann G . Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN. Proc Natl Acad Sci U S A. 2003; 100(7):3677-82. PMC: 152981. DOI: 10.1073/pnas.0737682100. View

Rutz S, Eidenschenk C, Ouyang W . IL-22, not simply a Th17 cytokine. Immunol Rev. 2013; 252(1):116-32. DOI: 10.1111/imr.12027. View

Zelante T, Fallarino F, Bistoni F, Puccetti P, Romani L . Indoleamine 2,3-dioxygenase in infection: the paradox of an evasive strategy that benefits the host. Microbes Infect. 2008; 11(1):133-41. DOI: 10.1016/j.micinf.2008.10.007. View

Kehl-Fie T, Skaar E . Nutritional immunity beyond iron: a role for manganese and zinc. Curr Opin Chem Biol. 2009; 14(2):218-24. PMC: 2847644. DOI: 10.1016/j.cbpa.2009.11.008. View

Barthel M, Hapfelmeier S, Quintanilla-Martinez L, Kremer M, Rohde M, Hogardt M . Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun. 2003; 71(5):2839-58. PMC: 153285. DOI: 10.1128/IAI.71.5.2839-2858.2003. View

Berger T, Togawa A, Duncan G, Elia A, You-Ten A, Wakeham A . Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2006; 103(6):1834-9. PMC: 1413671. DOI: 10.1073/pnas.0510847103. View

Crouch M, Castor M, Karlinsey J, Kalhorn T, Fang F . Biosynthesis and IroC-dependent export of the siderophore salmochelin are essential for virulence of Salmonella enterica serovar Typhimurium. Mol Microbiol. 2008; 67(5):971-83. DOI: 10.1111/j.1365-2958.2007.06089.x. View

Raffatellu M, Santos R, Verhoeven D, George M, Wilson R, Winter S . Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008; 14(4):421-8. PMC: 2901863. DOI: 10.1038/nm1743. View

Barman M, Unold D, Shifley K, Amir E, Hung K, Bos N . Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect Immun. 2007; 76(3):907-15. PMC: 2258829. DOI: 10.1128/IAI.01432-07. View

10.

Raffatellu M, George M, Akiyama Y, Hornsby M, Nuccio S, Paixao T . Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe. 2009; 5(5):476-86. PMC: 2768556. DOI: 10.1016/j.chom.2009.03.011. View

11.

Conti H, Shen F, Nayyar N, Stocum E, Sun J, Lindemann M . Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med. 2009; 206(2):299-311. PMC: 2646568. DOI: 10.1084/jem.20081463. View

12.

Poulsen K, Faith N, Steinberg H, Czuprynski C . Bacterial load and inflammation in fetal tissues is not dependent on IL-17a or IL-22 in 10-14 day pregnant mice infected with Listeria monocytogenes. Microb Pathog. 2012; 56:47-52. PMC: 3578105. DOI: 10.1016/j.micpath.2012.11.003. View

13.

Esser C, Rannug A, Stockinger B . The aryl hydrocarbon receptor in immunity. Trends Immunol. 2009; 30(9):447-54. DOI: 10.1016/j.it.2009.06.005. View

14.

Zheng Y, Valdez P, Danilenko D, Hu Y, Sa S, Gong Q . Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008; 14(3):282-9. DOI: 10.1038/nm1720. View

15.

Muhl H, Bachmann M, Pfeilschifter J . Inducible NO synthase and antibacterial host defence in times of Th17/Th22/T22 immunity. Cell Microbiol. 2011; 13(3):340-8. DOI: 10.1111/j.1462-5822.2010.01559.x. View

16.

Graham A, Carr K, Sieve A, Indramohan M, Break T, Berg R . IL-22 production is regulated by IL-23 during Listeria monocytogenes infection but is not required for bacterial clearance or tissue protection. PLoS One. 2011; 6(2):e17171. PMC: 3039664. DOI: 10.1371/journal.pone.0017171. View

17.

Whitehead R, VanEeden P, Noble M, Ataliotis P, Jat P . Establishment of conditionally immortalized epithelial cell lines from both colon and small intestine of adult H-2Kb-tsA58 transgenic mice. Proc Natl Acad Sci U S A. 1993; 90(2):587-91. PMC: 45708. DOI: 10.1073/pnas.90.2.587. View

18.

Feinen B, Russell M . Contrasting Roles of IL-22 and IL-17 in Murine Genital Tract Infection by Neisseria gonorrhoeae. Front Immunol. 2012; 3:11. PMC: 3342391. DOI: 10.3389/fimmu.2012.00011. View

19.

Wilson M, Feng C, Barber D, Yarovinsky F, Cheever A, Sher A . Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections. J Immunol. 2010; 184(8):4378-90. PMC: 3170015. DOI: 10.4049/jimmunol.0903416. View

20.

Hohmann E . Nontyphoidal salmonellosis. Clin Infect Dis. 2001; 32(2):263-9. DOI: 10.1086/318457. View