The Type I Interferon Receptor is Not Required for Protection in the Chlamydia and HSV-2 Murine Super-infection Model

Abstract

Chlamydia trachomatis/HSV-2 vaginal co-infections are seen clinically, suggesting that these sexually transmitted pathogens may interact. We previously established an intravaginal Chlamydia muridarum/HSV-2 super-infection model and observed that chlamydial pre-infection protects mice from a subsequent lethal HSV-2 challenge. However, the mechanism of protection remains unknown. The type I interferon, IFN-β, binds to the type I interferon receptor (IFNR), elicits a host cellular antiviral response and inhibits HSV replication in vitro and in vivo. Previous studies have demonstrated that C. muridarum infection stimulates genital tract (GT) IFN-β production; therefore, we hypothesized that chlamydial pre-infection protects mice from HSV-2 challenge via the IFN-β/IFNR-induced antiviral response. To test this prediction, we quantified IFN-β levels in vaginal swab samples. Detection of IFN-β in C. muridarum singly infected, but not in mock-infected animals, prompted the use of the super-infection model in IFNR knockout (IFNR−/−) mice. We observed that C. muridarum pre-infection reduces HSV-2-induced mortality by 40% in wild-type mice and by 60% IFNR−/− mice. Severity of HSV-2 disease symptoms and viral shedding was also similarly reduced by C. muridarum pre-infection. These data indicate that, while chlamydial infection induces GT production of IFN-β, type I IFN-induced antiviral responses are likely not required for the observed protective effect.

Isolation of a Chlamydia Strain from Lung Tissue Samples in Healthy Chickens Exhibiting Antagonistic Effects on Avian Infectious Bronchitis Virus

“…Our U-tube experiments also demonstrated that its antiviral effect is unrelated to the host's immune system. Notably, Slade et al's study showed that the antiviral effect of Cm wiess strain against HSV-2 does not work by stimulating host secretion of IFN- [15] .…”

“…Additionally, our results show that Chlamydia's antagonistic effect on related viruses is cell-autonomous. Slade et al's study suggests that the antiviral effect of Cm is density-dependent, requiring viable Cm (or its components) to exist in the early stages of infection in the host without relying on stimulating the host to secrete antiviral IFN- [14,15] . Previous studies on the antiviral mechanism of Wolbachia in the host has demonstrated that its antiviral effect is also cell-autonomous and relies on the distribution density of Wolbachia in the host.…”

Interferon profile of the mucosal immunity in women with papillomavirus infection

“…Регуляторную функцию ИФН-β способен реализовывать через модуляцию TLR-зависимого иммунного ответа, запуская каскад противовирусных реакций. Это послужило формированию мнения, что изолированный дефицит данного звена интерфероновой системы не играет клинически значимой роли при инфекционном поражении [9]. Основываясь на результатах нашего исследования, можно сделать вывод, что, несмотря на большее изменение уровня ИФН-β в группе с ПВИ и хламидийной инфекцией, уровень ИФН-γ в данной группе изменялся в меньшей степени, что, безусловно, требует дальнейшего изучения с позиции перекрестных взаимодействий ИФН.…”