Complement factor C5 but not C3 contributes significantly to hydrosalpinx development in mice infected with Chlamydia muridarum.

Abstract

Hydrosalpinx is a pathological hallmark of tubal infertility associated with chlamydial infection. However, the mechanisms of hydrosalpinx remain unknown. Here, we report that complement factor 5 (C5) contributes significantly to chlamydial induction of hydrosalpinx. Mice lacking C5 (C5(-/-)) failed to develop any hydrosalpinx, while ∼42% of the corresponding wild-type mice (C5(+/+)) did so following intravaginal infection with Chlamydia muridarum. Surprisingly, deficiency in C3 (C3(-/-)), an upstream component of the complement system, did not affect mouse susceptibility to chlamydial induction of hydrosalpinx. Interestingly, C5 activation was induced by chlamydial infection in oviducts of C3(-/-) mice, explaining why the C3(-/-) mice remained susceptible to chlamydial induction of hydrosalpinx. Similar levels of live chlamydial organisms were recovered from oviduct tissues of both C5(-/-) and C5(+/+) mice, suggesting that C5 deficiency did not affect C. muridarum ascending infection. Furthermore, C5(-/-) mice were still more resistant to hydrosalpinx induction than C5(+/+) mice, even when live C. muridarum organisms were directly delivered into the upper genital tract, both confirming the role of C5 in promoting hydrosalpinx and indicating that the C5-facilitated hydrosalpinx was not due to enhancement of ascending infection. The C5(-/-) mice displayed significantly reduced lumenal inflammatory infiltration and cytokine production in oviduct tissue, suggesting that C5 may contribute to chlamydial induction of hydrosalpinx by enhancing inflammatory responses.