The p47phox deficiency significantly attenuates the pathogenicity of Chlamydia muridarum in the mouse oviduct but not uterine tissues

Abstract

The Chlamydia muridarum induction of the upper genital tract pathology in mice has been used to investigate the mechanisms of chlamydial pathogenesis. We report that the NCF1 (neutrophil cytosolic factor1)-encoded p47phox (phagocyte oxidase), an essential subunit of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, contributes significantly to C. muridarum induction of hydrosalpinx. Mice lacking p47phox (p47phox-deficient) were no longer able to develop significant hydrosalpinx following an intravaginal infection with C. muridarum. However, there was no significant difference in uterine horn dilation (as a result of the endometrial glandular duct dilation) between the p47phox-deficient and -sufficient mice. Thus, the role of NADPH oxidase in chlamydial pathogenesis is restricted to the oviduct tissue rather than the entire upper genital tract. Interestingly, both the p47phox-deficient and -sufficient mice displayed similar levels of chlamydial live organism shedding from the lower genital tract, suggesting that the NADPH oxidase is not required for the mouse control of chlamydial infection in the lower genital tract. Furthermore, the p47phox deficiency did not affect the infectious organism burden in the upper genital tract tissues, indicating that the NADPH-oxidase activity is not necessary for the mouse prevention of chlamydial ascension from the lower to upper genital tracts. However, the p47phox-defieicnt mice displayed a significantly reduced chronic inflammatory infiltration in the oviduct but not uterine tissues, supporting the finding that the NADPH oxidase activity is required for chlamydial induction of dilation in the oviduct but not the endometrial glandular duct. Thus, we have demonstrated a significant role of the host NADPH oxidase in promoting chronic inflammatory pathology in the oviduct following chlamydial infection.