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A MyD88-Dependent Early IL-17 Production Protects Mice against Airway Infection with the Obligate Intracellular Pathogen Chlamydia muridarum¹

Xiaoyun Zhang^*,, Lifen Gao^*, Lei Lei^*, Youmin Zhong^*, Peter Dube^*, Michael T. Berton^*, Bernard Arulanandam, Jinshun Zhang and Guangming Zhong^2,*

^* Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229; Department of Biology, University of Texas, San Antonio, TX 78249; and Department of Biochemistry, Hebei North University, Zhangjiakou Hebei, China

We found that IL-17, a signature cytokine of Th17, was produced early in the innate immunity phase after an intranasal infection with the obligate intracellular pathogen Chlamydia muridarum. The airway IL-17, which peaked at 48 h after infection, was dependent on live chlamydial organism replication and MyD88-mediated signaling pathways. Treatment with antibiotics or knockout of the MyD88 gene, but not Toll/IL receptor domain-containing adapter-inducing IFN-β, can block the early IL-17 production. Treatment of mice with an anti-IL-17-neutralizing mAb enhanced growth of chlamydial organisms in the lung, dissemination to other organs, and decreased mouse survival, whereas treatment with an isotype-matched control IgG had no effect. Although IL-17 did not directly affect chlamydial growth in cell culture, it enhanced the production of other inflammatory cytokines and chemokines by Chlamydia-infected cells and promoted neutrophil infiltration in mouse airways during chlamydial infection, which may contribute to the antichlamydial effect of IL-17. These observations suggest that an early IL-17 response as an innate immunity component plays an important role in initiating host defense against infection with intracellular bacterial pathogens in the airway.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants (to G.Z.) from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Guangming Zhong, Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229. E-mail address: Zhongg{at}uthscsa.edu

³ Abbreviations used in this paper: Wt, wild type; TRIF, Toll/IL receptor domain-containing adapter-inducing IFN-β; IFU, inclusion-forming unit; BALF, bronchial alveolar lavage fluid; KO, knockout.