THE EFFECTS OF VIRAL DOSE ON THE KINETICS OF ADAPTIVE AND INNATE IMMUNE RESPONSE DURING INTRAVAGINAL INFECTION
Miles Oliva1,2, Shomyseh Sanjabi3.
1University of California, San Francisco, San Francisco, CA, 2Columbia Pacific University, San Francisco, CA, 3Gladstone Institutes, San Francisco, CA.
Innate and adaptive immunity defends against viral infections in mammals. CD8 T-cells, an essential component of adaptive immunity, must expand in number quickly enough to successfully suppress viral load. In the study of HIV, it is believed that during mucosal infection, CD8 T-cell response is delayed and dampened compared with systemic infection. Using lymphocytic choriomeningitis virus (LCMV), the Sanjabi lab has evidence that a sub-optimal innate immune activation is responsible for this defect in CD8 T-cell response after vaginal viral infection. This may be due either to the tolerogenic mucosal environment that inhibits increased innate immune activation, or due to inefficiency in viral transmission across the mucosal barrier. However, it is still unknown why a mucosal infection elicits a delayed and diminished immune response. To address these possibilities, we vaginally infected three cohorts of mice with different doses of LCMV (1x, 2x, or 4x viral load per mouse, respectively), and monitored each cohort’s innate and adaptive immune activation in the female reproductive tract (FRT), draining lymph nodes, spleen, and peripheral blood lymphocytes. We have found that, during the period from 3 to 5 days after infection, the lower FRT experiences an increase in viral load while the iliac lymph node begins to clear the virus. Furthermore, increasing viral doses leads to more robust and faster CD8 T-cell responses. These results further confirm that the FRT environment inhibits efficient immune response and that increasing viral titrations alters CD8 T-cell kinetics.