Potential role for CD169+ macrophages in colon infection and inflammation following systemic murine CMV (MCMV) administration 4208

Abstract Description While cytomegalovirus (CMV) rarely induces colitis in immunocompetent individuals, CMV reactivation is a primary cause of colitis in immunocompromised patients. However, the mechanisms by which CMV infects the colon, promotes inflammation, and establishes latency are unclear. We characterized infection of the colon following intraperitoneal administration with OVA-peptide (SIINFEKL)-expressing MCMV. As previously reported, the viral load in colon tissue peaked at 5 days post infection (dpi). Recruited early, neutrophil and inflammatory monocyte (IM) levels peaked at 5 dpi, with 6-fold (p < 0.001) and 23-fold increases (p < 0.0001), respectively, relative to naïve mice. γδ T cell presence increased at 5 dpi and CD8ab+ T cells reached peak levels at 7 dpi (14-fold increase, p = 0.001). Prior studies found that colonic macrophages (cMPs) avidly capture antigens from the blood and that the CD169+ cMP subpopulation provides inflammatory chemokines during acute DSS colitis. Preliminary results indicate that CD169+ cMP-depleted transgenic mice had reduced IM infiltration (7-fold decrease, p < 0.001) and tended to have lower viral loads, compared with littermate controls (n = 4). Importantly, CD169+ cMP in wildtype mice presented SIINFEKL peptide on MHCI throughout active infection. Together, these data describe the inflammation in the colon following systemic MCMV infection and suggest a role for CD169+ cMPs in virus uptake, induction of inflammation, and antigen presentation in this model. Funding Sources Supported by funding from Division of Intramural Research at NIAID/NIH. Topic Categories Mucosal and Regional Immunology (MUC)