Complement factor C5 but not C3 contributes significantly to hydrosalpinx development in mice infected with Chlamydia muridarum.
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.
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Zhangsheng
Z
Yang
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Turner
T
Conrad
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Zhou
Z
Zhou
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Jianlin
J
Chen
Institute of Medical Microbiology and Hospital Epidemiology/Medical School Hannover (MHH), Hannover, Germany.
Pavel
P
Dutow
Institute of Medical Microbiology and Hospital Epidemiology/Medical School Hannover (MHH), Hannover, Germany.
Andreas
A
Klos
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Zhongg@UTHSCSA.edu.
Guangming
G
Zhong
D000818:Animals; D002690:Chlamydia Infections / Q000382:microbiology* / Q000473:pathology*; D023502:Chlamydia muridarum / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology*; D003182:Complement C5 / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D012488:Salpingitis / Q000382:microbiology* / Q000473:pathology*
D003176:Complement C3; D003182:Complement C5