Mosquito saliva alters draining LN architecture and function

Abstract Current murine models of most arbovirus infections result in the development of viremia and antiviral adaptive immune responses. However, delivery of virus by injection via syringe does not fully encompass all aspects of the response that develops after viral delivery via mosquito bite. One reason for this is likely to be the lack of additional immunomodulatory responses specifically induced by mosquito saliva as previous studies have demonstrated profound proviral and immunosuppressive properties of saliva. While the adaptive antiviral response develops in the lymph node draining the site of infection, the impact of mosquito saliva on this critical lymphoid organ has not been extensively explored. Further, the lymphatic system acts both as centralized hubs for immune cell activation and as dissemination pathways to distal tissues, meaning that immunomodulation of the lymphatic system likely affects infection and immunity systemically. Therefore, we explored the effect of mosquito saliva on the structure and function of the draining lymph node in the presence of absence of the mosquito borne arbovirus Zika virus (ZIKV). Preliminary confocal microscopic analyses of lymph nodes after saliva injection into the skin revealed changes in nodal architecture and specific cellular populations. Future studies will explore the impact of saliva specifically on lymphatic endothelial cells within the lymph node. These studies should provide additional insight into the mechanisms of bite-induced immunomodulation in secondary lymphoid organs and the impact on the developing antiviral response. Supported by the Intramural Research Program of NIAID, NIH (H.D.H.)