Chlamydia-Specific CD8+ T cells Enhance Neutrophil Infiltration into Chlamydia-Infected Female Mouse Genital Tract

Abstract

Abstract We recently demonstrated that Chlamydia-specific TNF-α producing and TNF receptor 2 bearing CD8+ T cells mediate chlamydial pathogenesis in the mouse female upper genital tract (UGT). Additionally, TNF-α production from CD8+ T lymphocytes is necessary for pathogenesis; however, CD8+ T lymphocytes are not a sufficient source of TNF-α production for pathogenesis. Myeloid cells including neutrophils are important sources of TNF-α production and have been implicated in chlamydial pathogenesis. Herein, we evaluated frequency of neutrophils in Chlamydia muridarum-infected female genital tracts of C57BL/6J (WT) mice, mice deficient in Chlamydia-specific CD8+ T cells (OT-1 mice) and TNFR2 knockout (KO) mice. Frequencies of Gr-1+ cells (neutrophils) in UGT were evaluated on days 4, 9, 15, and 24 following genital Chlamydia muridarum infection. OT-1 and TNFR2 KO displayed significant reduction in neutrophil frequency compared to WT animals on day 9 following chlamydial inoculation. Furthermore, we found that OT-1 mice replete with WT CD8+ T cells at the time of chlamydial inoculation display restoration of neutrophil (Ly-6G) frequency to WT levels. These results suggest that Chlamydia-specific CD8+ T cells engage other inflammatory cells such as neutrophils in infected genital tracts in order to cause chronic pathologies in the upper reproductive tract.