A MyD88-dependent early IL-17 production protects mice against airway infection with the obligate intracellular pathogen Chlamydia muridarum.
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-beta, 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.
Zhang
Xiaoyun
X
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Gao
Lifen
L
Lei
Lei
L
Zhong
Youmin
Y
Dube
Peter
P
Berton
Michael T
MT
Arulanandam
Bernard
B
Zhang
Jinshun
J
Zhong
Guangming
G
D000818:Animals; D023502:Chlamydia muridarum / Q000254:growth & development; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000502:physiology*; D020556:Neutrophil Infiltration; D012141:Respiratory Tract Infections / Q000276:immunology*; D015996:Survival Rate; D013997:Time Factors
D016207:Cytokines; D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88