B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection

• DOI: 10.1038/s41385-018-0009-4
• Publication Date: 2018-02-15T00:10:16Z
• Authors: Martin Trapecar; Shahzada Khan; Benjamin L. Cohn; Frank Wu; Shomyseh Sanjabi
• Keywords: Colon; Knockout; Immunology; 610; Inbred C57BL; Lymphocyte Activation; Medical and Health Sciences; Article; Mice; 03 medical and health sciences; Cell Movement; Biodefense; 616; 2.1 Biological and endogenous factors; Innate; Animals; Arenaviridae Infections; Lymphocytic choriomeningitis virus; Lymphocytes; Mice, Knockout; B-Lymphocytes; 0303 health sciences; Biomedical and Clinical Sciences; Inflammatory and immune system; Immunity; Rectum; Biological Sciences; Immunity, Innate; 3. Good health; Mice, Inbred C57BL; Infectious Diseases; Emerging Infectious Diseases; Good Health and Well Being; Medical Microbiology; Vagina; HIV/AIDS; Sexually Transmitted Infections; Female; Digestive Diseases; Infection

Determining the magnitude of local immune response during mucosal exposure to viral pathogens is critical to understanding the mechanism of viral pathogenesis. We previously showed that vaginal inoculation of lymphocytic choriomeningitis virus (LCMV) fails to induce a robust innate immune response in the lower female reproductive tract (FRT), allowing high titer viral replication and a delay in T-cell-mediated viral control. Despite this immunological delay, LCMV replication remained confined mainly to the FRT and the draining iliac lymph node. Here, we show that rectal infection with LCMV triggers type I/III interferon responses, followed by innate immune activation and lymphocyte recruitment to the colon. In contrast to vaginal exposure, innate immunity controls LCMV replication in the colon, but virus rapidly disseminates systemically. Virus-induced inflammation promotes the recruitment of LCMV target cells to the colon followed by splenic viral dissemination by infected B cells, and to a lesser extent by CD8 T cells. These findings demonstrate major immunological differences between vaginal and rectal exposure to the same viral pathogen, highlighting unique risks associated with each of these common routes of sexual viral transmission.