Chlamydia Lipooligosaccharide Has Varied Direct and Indirect Roles in Evading both Innate and Adaptive Host Immune Responses

Abstract

Chlamydia bacteria are obligate intracellular pathogens which can cause a variety of disease in humans and other vertebrate animals. To successfully complete its life cycle, Chlamydia must evade both intracellular innate immune responses and adaptive cytotoxic T cell responses. Here, we report on the role of the chlamydial lipooligosaccharide (LOS) in evading the immune response. Chlamydia infection is known to block the induction of apoptosis. However, when LOS synthesis was inhibited during Chlamydia trachomatis infection, HeLa cells regained susceptibility to apoptosis induction following staurosporine treatment. Additionally, the delivery of purified LOS to the cytosol of cells increased the levels of the antiapoptotic protein survivin. An increase in survivin levels was also detected following C. trachomatis infection, which was reversed by blocking LOS synthesis. Interestingly, while intracellular delivery of lipopolysaccharide (LPS) derived from Escherichia coli was toxic to cells, LOS from C. trachomatis did not induce any appreciable cell death, suggesting that it does not activate pyroptosis. Chlamydial LOS was also a poor stimulator of maturation of bone marrow-derived dendritic cells compared to E. coli LPS. Previous work from our group indicated that LOS synthesis during infection was necessary to alter host cell antigen presentation. However, direct delivery of LOS to cells in the absence of infection did not alter antigenic peptide presentation. Taken together, these data suggest that chlamydial LOS, which is remarkably conserved across the genus Chlamydia, may act both directly and indirectly to allow the pathogen to evade the innate and adaptive immune responses of the host.

Host cell death during infection withChlamydia: a double-edged sword

“… 2019 ). The low toxicity of C. trachomatis L2 LPS upon transfection was confirmed in a more recent study (Wang, Rockey and Dolan 2020 ).…”

“… 2009 ). LPC-011, which blocks the synthesis of LPS by inhibiting the enzyme UDP-3-O-(R-3-hydroxymyristoyl)- N -acetylglucosamine deacetylase (LPXC), also sensitized cells infected with C. trachomatis to STS-induced apoptosis (Wang, Rockey and Dolan 2020 ). Yet the inhibitor is also known to induce abnormal bacterial development and to block inclusion formation when used at high concentrations (Nguyen et al .…”

Psittacosis: An Underappreciated and Often Undiagnosed Disease

“…It is noteworthy that much of the research on the immune response to Chlamydia infections is from C. trachomatis, the most frequently reported sexually transmitted infection (STI) in the US [ 20 ]. In the course of its life cycle, Chlamydia evades both intracellular innate immune responses and adaptive cytotoxic T cell responses [ 21 , 22 ]. Chlamydial lipooligosaccharide (LOS) has a direct role in immune evasion and is conserved throughout the Chlamydia genus.…”

Insights into innate immune cell evasion by Chlamydia trachomatis

“…Recent studies indicate that C. trachomatis uses effector molecules like GarD that helps it to escape immune surveillance via avoiding ubiquitination and proteosomal degradation ( 23 , 24 ). Recent findings indicate that Chlamydial lipopolysaccharide (LPS) ( 25 ) and lipooligosaccharide (LOS) ( 26 ) do not readily trigger innate inflammatory pathways, thus avoiding early innate recognition and promoting its survival and multiplication.…”