IL-22 Mediates Mucosal Host Defense Against Gram-negative Bacterial Pneumonia

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2008 Feb 12

PMID 18264110

Citations 621

Authors

Shean J Aujla

Yvonne R Chan

Mingquan Zheng

Mingjian Fei

David J Askew

Derek A Pociask

Todd A Reinhart

Florencia McAllister

Jennifer Edeal

Kristi Gaus

Shahid Husain

James L Kreindler

Patricia J Dubin

Joseph M Pilewski

Mike M Myerburg

Carol A Mason

Yoichiro Iwakura

Jay K Kolls

Affiliations

Soon will be listed here.

Abstract

Emerging evidence supports the concept that T helper type 17 (T(H)17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T(H)17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony-stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury. These data support the concept that the T(H)17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.

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References

Wilson N, Boniface K, Chan J, McKenzie B, Blumenschein W, Mattson J . Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007; 8(9):950-7. DOI: 10.1038/ni1497. View

Langrish C, McKenzie B, Wilson N, De Waal Malefyt R, Kastelein R, Cua D . IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev. 2004; 202:96-105. DOI: 10.1111/j.0105-2896.2004.00214.x. View

Mangan P, Harrington L, OQuinn D, Helms W, Bullard D, Elson C . Transforming growth factor-beta induces development of the T(H)17 lineage. Nature. 2006; 441(7090):231-4. DOI: 10.1038/nature04754. View

Franks T, Chong P, Chui P, Galvin J, Lourens R, Reid A . Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore. Hum Pathol. 2003; 34(8):743-8. PMC: 7119137. DOI: 10.1016/s0046-8177(03)00367-8. View

Liang S, Tan X, Luxenberg D, Karim R, Dunussi-Joannopoulos K, Collins M . Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006; 203(10):2271-9. PMC: 2118116. DOI: 10.1084/jem.20061308. View

Shibata K, Yamada H, Hara H, Kishihara K, Yoshikai Y . Resident Vdelta1+ gammadelta T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production. J Immunol. 2007; 178(7):4466-72. DOI: 10.4049/jimmunol.178.7.4466. View

Acosta-Rodriguez E, Napolitani G, Lanzavecchia A, Sallusto F . Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol. 2007; 8(9):942-9. DOI: 10.1038/ni1496. View

Ye P, Rodriguez F, Kanaly S, Stocking K, Schurr J, Schwarzenberger P . Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001; 194(4):519-27. PMC: 2193502. DOI: 10.1084/jem.194.4.519. View

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

10.

Veldhoen M, Hocking R, Atkins C, Locksley R, Stockinger B . TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006; 24(2):179-89. DOI: 10.1016/j.immuni.2006.01.001. View

11.

Singh P, Jia H, Wiles K, Hesselberth J, Liu L, Conway B . Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A. 1998; 95(25):14961-6. PMC: 24558. DOI: 10.1073/pnas.95.25.14961. View

12.

Kao C, Chen Y, Thai P, Wachi S, Huang F, Kim C . IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol. 2004; 173(5):3482-91. DOI: 10.4049/jimmunol.173.5.3482. View

13.

Zenewicz L, Yancopoulos G, Valenzuela D, Murphy A, Karow M, Flavell R . Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity. 2007; 27(4):647-59. PMC: 2149911. DOI: 10.1016/j.immuni.2007.07.023. View

14.

Malley R, Srivastava A, Lipsitch M, Thompson C, Watkins C, Tzianabos A . Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide. Infect Immun. 2006; 74(4):2187-95. PMC: 1418935. DOI: 10.1128/IAI.74.4.2187-2195.2006. View

15.

You Y, Richer E, Huang T, Brody S . Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population. Am J Physiol Lung Cell Mol Physiol. 2002; 283(6):L1315-21. DOI: 10.1152/ajplung.00169.2002. View

16.

Dumoutier L, Louahed J, Renauld J . Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J Immunol. 2000; 164(4):1814-9. DOI: 10.4049/jimmunol.164.4.1814. View

17.

Chung D, Kasper D, Panzo R, Chitnis T, Grusby M, Sayegh M . CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol. 2003; 170(4):1958-63. DOI: 10.4049/jimmunol.170.4.1958. View

18.

Chakinala M, Trulock E . Pneumonia in the solid organ transplant patient. Clin Chest Med. 2005; 26(1):113-21. DOI: 10.1016/j.ccm.2004.10.010. View

19.

Langrish C, Chen Y, Blumenschein W, Mattson J, Basham B, Sedgwick J . IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005; 201(2):233-40. PMC: 2212798. DOI: 10.1084/jem.20041257. View

20.

Higgins S, Jarnicki A, Lavelle E, Mills K . TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J Immunol. 2006; 177(11):7980-9. DOI: 10.4049/jimmunol.177.11.7980. View