Chlamydiae are obligate intracellular bacteria which cause multiple human diseases.No vaccine is avail able for human chlamydial infections.Better understanding on the protective mechanisms of chlamydial infections is important for rational development of an effective and safe vaccine.Studies in recent years have demonstrated the importance of Th1 and Th17 responses in host defense against chlamydial infection.ICOS is a CD28 family molecule which mainly expresses on activated T cells.The only ligand of ICOS,ICOSL,expressed on dendritic cells (DCs), B cells and some other cell types.Our data showed that Th17, but not Th 1, response are dependent on ICOSL/ICOS interaction between DC and T cells.Both ICOS and ICOSL gene knockout (KO) mice show dra matically reduced Th17 response,but normal or even higher Th1 response.Both KO mice show exacerbated dis ease and increased chlamydial grow in vivo.In addition, most of the Th17 cells are ICOS+ ,while most of the Th1cells are ICOS-following chlamydial infection.Moreover,IL-10 KO mice show better protection than wild-type mice with higher Th17 response and higher ICOSL expression on DCs.Blockade of Il-17 in vivo virtually abol ished the better protection in IL-10 KO mice.Furthermore,partial ICOS mutant mice with deficiency in PI3K pathway showed intermediate reduction of Th17 response and protection,suggesting that calcium pathway is also involved in the Th17 development and protection.Further,ICOS/ICOSL interaction is critical for the production Th17 promoting cytokines and RORγt,the transcription factor for Th17.The results suggest that ICOS signaling is critical for the development of Th17 responses and that the balance of Th1 and Th17 is crucial for host defense against chlamydial infection.