IL-17/Th17 promotes type 1 T cell immunity against pulmonary intracellular bacterial infection through modulating dendritic cell function.

Abstract

Although their contribution to host defense against extracellular infections has been well defined, IL-17 and Th17 are generally thought to have limited impact on intracellular infections. In this study, we investigated the role and mechanisms of IL-17/Th17 in host defense against Chlamydia muridarum, an obligate intracellular bacterium, lung infection. Our data showed rapid increase in IL-17 production and expansion of Th17 cells following C. muridarum infection and significant detrimental impact of in vivo IL-17 neutralization by anti-IL-17 mAb on disease course, immune response, and dendritic cell (DC) function. Specifically, IL-17-neutralized mice exhibited significantly greater body weight loss, higher organism growth, and much more severe pathological changes in the lung compared with sham-treated control mice. Immunological analysis showed that IL-17 neutralization significantly reduced Chlamydia-specific Th1 responses, but increased Th2 responses. Interestingly, the DC isolated from IL-17-neutralized mice showed lower CD40 and MHC II expression and IL-12 production, but higher IL-10 production compared with those from sham-treated mice. In two DC-T cell coculture systems, DC isolated from IL-17-neutralized mice induced higher IL-4, but lower IFN-gamma production by Ag-specific T cells than those from sham-treated mice in cell priming and reaction settings. Adoptive transfer of DC isolated from IL-17-neutralized mice, unlike those from sham-treated mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that IL-17/Th17 plays an important role in host defense against intracellular bacterial infection, and suggest that IL-17/Th17 can promote type 1 T cell immunity through modulating DC function.

• Authors: Hong Bai, Jianjun Cheng, Xiaoling Gao, Antony George Joyee, Yijun Fan, Shuhe Wang, Lei Jiao, Zhi Yao, Xi Yang
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 9 Pg. 5886-95 (Nov 01 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19812198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17

Topics

• Animals
• Cells, Cultured
• Chlamydia Infections (immunology, microbiology, pathology)
• Chlamydia muridarum (immunology)
• Coculture Techniques
• Dendritic Cells (immunology, microbiology, pathology)
• Female
• Immunity, Cellular
• Interleukin-17 (antagonists & inhibitors, immunology, physiology)
• Intracellular Fluid (immunology, microbiology)
• Lung (immunology, microbiology, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Pneumonia, Bacterial (immunology, microbiology, pathology)
• Th1 Cells (immunology, metabolism, microbiology)