Environmental factors, such as viral infections, are proposed to damage pancreatic beta-cells and confer risk for autoimmune diabetes pathogenesis. Encephalomyocarditis virus (EMCV) is a positive single-stranded RNA picornavirus that induces diabetes in genetically susceptible mice. EMCV-induced diabetes is associated with macrophage activation and the expression of pro-inflammatory mediators such as interleukin-1 (IL-1beta) and nitric oxide (a product of inducible nitric oxide synthase – iNOS). We have recently identified the chemokine receptor CCR5 as a required signaling receptor for EMCV-stimulated inflammatory gene induction (iNOS, IL-1beta, and COX-2) in macrophages. The CCR5-dependent signaling mechanisms that regulate macrophage responses to virus infection is currently being examined.
Wang, Y., Shaked, I., Stanford, S.M., Zhou, W., Curtsinger, J.M., Mikulski, Z., Shaheen, Z.R., Cheng, G., Sawatzke, K., Campbell, A.M., Auger, J.L., Bilgic, H., Shoyama, F.M., Schmeling, D.O., Balfour Jr., H.H., Hasegawa, K., Chan, A.C., Corbett, J.A., Binstadt, B.A., Mescher, M.F., Ley, K., Bottini, N., Peterson, E. (2013) The autoimmunity-associated gene Ptpn22 potentiates Toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity 39(1), 111-122