Main Research Areas

Effect of Sex hormones on mucosal immunity to sexually transmitted diseases.

Sexually transmitted diseases (STDs) are one of the leading causes of morbidity worldwide and a substantial drain on the health system of both developing and developed countries. Despite limited success of drug therapies, the best solution for long term control of STDs is to develop efficacious vaccines. An effective vaccine for both bacterial and viral STD has to target induction of protective immunity in the genital tract, where the pathogens first come into contact with the body. In order to design successful vaccine strategies, we have to take into account factors that affect immunity in the genital mucosa.

We have previously shown that sex hormones, estradiol and progesterone, regulate the immune system in the female genital tract in a precise and differential manner. My research is currently directed at understanding the mechanism by which sex hormones regulate susceptibility and immune responses in the genital tract to both bacterial and viral sexually transmitted diseases (STDs). We are using a number of in vivo and in vitro models to elucidate these mechanisms.

One of the models that I have established, is a rat model for Chlamydia trachomatis, the leading cause of bacterial STDs. Using this system, we have shown that hormonal environment at the time of infection determines both susceptibility and immune responses to genital chlamydia infections. We found that in this model, progesterone increases susceptibility and inflammation while estradiol protects from infection and is anti-inflammatory. Currently we are trying to elucidate the underlying mechanisms of the hormone effects.

I have also recently set up a mouse model to examine the effect of hormones on genital herpes (HSV-2) infection. When mice are given different hormone combinations, they show dramatic changes in their susceptibility to genital HSV-2 infection. In order to understand these changes, we are starting to examine the expression of herpes receptors under different hormonal conditions. This will test the hypothesis that the alteration in susceptibility may be due to regulation of HSV receptors by sex hormones. We are also examining the chemokine expression in the genital tract before and after infection under different hormonal conditions.

Our studies on C.trachomatis and HSV-2 show that quite likely sex hormones will have similar effects on other infections in the genital tract. In a third project, we are planning to examine the effect of sex hormones on infectivity of and immune responses to human immunodeficiency virus (HIV) in the female genital tract. We will be using an in vitro model that mimics the interaction of HIV in the genital tract. Using endometrial carcinoma cell lines co-cultured with infected peripheral blood mononuclear cells, we will examine the effect of sex hormones on infectivity of HIV.

• Charu Kaushic, AD Murdin, F. Zhou, and C.R. Wira. Effect of route of infection on the susceptibility and immune responses to Chlamydia trachomatis infection in the female reproductive tract. (submitted)
  
   
• Charu Kaushic, F. Zhou , A.D. Murdin, and C.R. Wira. Effect of estradiol and progesterone on susceptibility and immune responses to Chlamydia trachomatis infection in the female reproductive tract. Infection and Immunity, 2000. 68 (7), 4207-16
   
• Charles R.Wira, Richard M. Rossoll and Charu Kaushic. Antigen presenting cells in the female reproductive tract: Influence of estrogen on antigen presentation by vaginal cells. Endocrinology, 2000. 141 (8), 2877-85
   
• Charu Kaushic, Katie Grant, Mardi Crane and C.R. Wira. Infectivity of human endometrial epithelial cells with Chlamydia trachomatis. American Journal of Reproductive Immunology, 2000. 44 (2) 73-79
   
• Charu Kaushic, Andrew D. Murdin, Brian J. Underdown, Charles R. Wira. Chlamydia trachomatis infection in the female reproductive tract of rat: Influence of progesterone on infectivity and immune response. Infection and Immunity. 1998. 66 (3), 893-898.