The impact of methamphetamine use on host immune response to herpes simplex virus type 2 (105.15)

Abstract

Abstract Methamphetamine (METH) use is associated with increased risk for sexually transmitted infections (STIs) that is not believed to be due to increased behavioral risk factors alone. However, the impact of METH at the time of exposure to an STI has not been explored. We hypothesized that METH would impact normal host immune responses to an STI pathogen, herpes simplex virus type 2 (HSV-2), resulting in alterations in disease. Female C57BL6 mice were treated with METH (10 mg/kg) or saline daily for 5 days, and inoculated intravaginally with HSV-2 on treatment day 3. METH treated mice experienced significantly earlier onset of disease and enhanced disease progression compared to controls. Unexpectedly, METH treated mice had increased IFNγ levels in the genital tract early after challenge, but this did not correlate with decreased vaginal virus titers. Subsequently, later after virus challenge there were significantly less IFNγ secreting CD4+ T cells in the genital tract of METH treated mice, but an increased number of these cells in the iliac lymph nodes. Our studies confirm our hypothesis that METH alters immune responses to intravaginal HSV-2 challenge with a corresponding impact on disease progression. The alterations in IFNγ production in the genital tract are of particular interest because of the important role of this cytokine in HSV-2 control. These findings have important public health implications and may be more broadly applicable to other important STI’s such as HIV.