CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation.

Yuyang Zhang,Guangming Zhong,Huihua Cai,Dongmei Zhang,Yuanli He,Donghua Sun,Siping Chen

doi:10.3855/jidc.9356

Abstract

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated. The pathological mechanisms of chlamydia-induced disease remain largely unknown, but it has been proposed that CPAF, a chlamydia-secreted serine protease, may play major roles in aiding chlamydial infection and contribute to chlamydia pathogenesis during in vivo infection. According to previous results, CPAF targets host immunity by degrading antimicrobial peptides and neutralizing complement activity; however, whether CPAF is involved in chlamydial antigen presentation has never been reported. Antigen presentation assay was used to monitor the effects of CPAF on OT1-, OT2-, and chlamydia T cell antigen-mediated antigen presentation. In vitro cell-free degradation assay was used to detect CPAF processing of chlamydia T cell antigens. We found that CPAF preferably inhibits OT2- but not OT1-mediated antigen presentation. CPAF inhibits OT2 antigen presentation by direct proteolytic cleavage in the wild type CPAF, but not enzymatic mutants. Importantly, several previously identified chlamydial T cell antigens were selectively degraded by CPAF when co-incubated in vitro. In addition, specific inhibition T cell antigen presentation by CPAF was correlated with T cell antigen cleavage by CPAF in vitro assay. Our experiments demonstrated that CPAF selectively and specifically degrades chlamydial T cell antigens, which chlamydia may utilize as a novel mechanism for evading host immune responses to promote chlamydia survival.

Highlights

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated
To test whether Chlamydial Protease-Like Activity Factor (CPAF) can inhibit antigen presentation, we monitored IL-2 production from the supernatant that was harvested from stimulated T cells, which indicates the activity of antigen presentation
To our surprise, when OT1 was replaced with OT2 to perform the same experiment, we found that even wt CPAF failed to inhibit any antigen presentation activity, showing that IL-2 production was similar between groups from OT1 with pre-incubation of wt CPAF or without preincubation of wt CPAF (Figure 1A, panel b, columns 5-8)

Summary

Introduction

Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated. In vitro cell-free degradation assay was used to detect CPAF processing of chlamydia T cell antigens. Several previously identified chlamydial T cell antigens were selectively degraded by CPAF when co-incubated in vitro. Conclusions: Our experiments demonstrated that CPAF selectively and degrades chlamydial T cell antigens, which chlamydia may utilize as a novel mechanism for evading host immune responses to promote chlamydia survival. Chlamydia trachomatis (C. trachomatis) infection in the lower genital tract (LGT) of women can lead to inflammatory pathologies such as hydrosalpinx in the upper genital tract (UGT), resulting in severe complications, including ectopic pregnancy and infertility [1,2,3]. To overcome the host immunity barriers, and establish the successful infection, chlamydia may utilize virulence factors as previously proposed [10]. It is known that C. trachomatis organisms can secrete numerous proteins into host cell cytoplasm

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Conclusion