Extrusion as a Mechanism of Host Immune Response Evasion in a Chlamydia trachomatis Murine Infection Model
Abstract
Chlamydia trachomatis is an obligate intracellular organism that is the leading cause of preventable blindness and sexually transmitted bacterial infections. C. trachomatis exhibits a biphasic developmental cycle involving infectious elementary bodies (EB) and non-infectious, replicative reticulate bodies (RBs). At the end of its developmental cycle, EBs disseminate to neighboring cells either via host cell lysis or a novel mechanism of exit, called extrusion. It has been hypothesized that extrusions serve as a means of immune response evasion due to enclosure within host membrane. In addition, extrusions filled with multiple EBs may serve as a mode for high dose delivery of infectious organisms to tissues, rather than individual EBs from lysed host cells. Herein, female mice were intra-vaginally infected with either a C. trachomatis serovar L2 wild type strain or a mutant strain containing a silenced CT228 gene, which produces significantly more extrusions in vitro, relative to the wild type. All mice were characterized for, i.) time course of infection, ii.) systemic and mucosal immune response to infection, iii.) degree of reproductive tissue damage following clearance of infection, and iv.) recruitment of different immune cell types to reproductive tracts. In comparison to the wild-type strain, mice infected with the mutant strain revealed an increase in the time needed to clear infection, a reduction in the systemic anti-Chlamydia antibodies, and a decrease in mucous production. However, there were no significant differences amongst the concentrations of immune cells recruited to the reproductive tracts. These data may suggest that EB antigen within extrusions dampen recognition by the immune system. Therefore, further research is warranted to quantitate cytokine concentrations, to examine antigen presentation, and to examine the development of protective immunity.
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- OSU Theses [15752]