| First Author | Rixon JA | Year | 2022 |
| Journal | PLoS Pathog | Volume | 18 |
| Issue | 2 | Pages | e1010333 |
| PubMed ID | 35196366 | Mgi Jnum | J:322503 |
| Mgi Id | MGI:6890010 | Doi | 10.1371/journal.ppat.1010333 |
| Citation | Rixon JA, et al. (2022) Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice. PLoS Pathog 18(2):e1010333 |
| abstractText | Protective immune responses to Chlamydia infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are believed to be vital for bacterial clearance due to their capacity to secrete IFN-gamma, but an essential requirement for T-bet-expressing Th1 cells has yet to be demonstrated in the mouse model of Chlamydia infection. Here, we investigated the role of T-bet and IFN-gamma in primary clearance of Chlamydia after FRT infection. Surprisingly, IFN-gamma producing CD4 T cells from the FRT expressed low levels of T-bet throughout infection, suggesting that classical T-bet-expressing Th1 cells are inefficiently generated and therefore unlikely to participate in bacteria clearance. Furthermore, mice deficient in T-bet expression or with a CD4-specific T-bet deficiency cleared FRT infection similarly to wild-type controls. T-bet-deficient mice displayed significant skewing of FRT CD4 T cells towards Th17 responses, demonstrating that compensatory effector pathways are generated in the absence of Th1 cells. In marked contrast, IFN-gamma-, and IFN-gammaR-deficient mice were able to reduce FRT bacterial burdens, but suffered systemic bacterial dissemination and 100% mortality. Together, these data demonstrate that IFN-gamma signaling is essential to protect mice from fatal systemic disease, but that classical T-bet-expressing Th1 cells are non-essential for primary clearance within the FRT. Exploring the protective contribution of Th1 cells versus other CD4 effector lineages could provide important information for the generation of new Chlamydia vaccines. |
