HPV16 E6/E7 proteins alters the development of Chlamydia trachomatis and could be related to the persistence of the bacteria

Washington

Conferencia; 35th International Papillomavirus Conference - IPVC 2023; 2023

INTRODUCTION HPV and Chlamydia trachomatis (Ct) are highly prevalent sexually transmitted infections worldwide being the coinfection with these two pathogens a frequent finding in clinical practice. Research has shown that HPV is causative of cancer and Ct a potential cofactor in the development cellular transformation. However, the understanding on this coinfection and its mechanisms are still unclear. The aim of the present study was to evaluate the impact that two important proteins (E6 and E7) of HPV-16 would have on Ct development.METHODS Carcinoma endocervical C33-A cells expressing or not E6/E7 proteins from high-risk HPV 16 were infected with Ct LGV-L2 strain for 24 or 40 hours. Ct inclusions size and number were determined by immunofluorescence microscopy using chlamydia specific antibodies (CT043). Flow cytometry was used to analyzed the expression of immune co-inhibitory molecules in C33A and C33E6E7 cells infected or not with Ct.RESULTS Ct development in C33-A cells expressing E6/E7 proteins showed a different pattern when compared to Ct development in C33-A cells. Certainly, intracellular development of Ct in C33-E6E7 cells yield smaller inclusions size at both times analyzed (poner datos xxxxxxp<0.01). Furthermore, generation of infectious progeny from C33E6E7 infected cells showed a significant reduction when compared to those from C33-A cells, both results supporting the presence of Chlamydial persistence. In addition, we found that C33E6E7 cells express higher levels of the co-inhibitory molecules PD-1, PD-L1, CD160 and HVEM and infection with Ct enhanced even more the inhibitory molecules expression.CONCLUSIONOur results show that in the presence of HPV E6/E7 proteins Ct goes into a persistence state and induces an enhanced expression of co-inhibitory molecules, both findings that could decline the induction of an accurate immune response and could facilized a disease exacerbation.