The regulation of anti-microbial inflammatory responses is necessary for clearance of infection and prevention of overt pathology in the midst of these responses. While the induction of regulatory cytokines such as interleukin 10 (IL-10) can be beneficial to this end, pathogens have evolved to induce these host cytokines to avert immediate immune mediated elimination. Cytomegalovirus has been shown to induce the production of host IL-10 and the presence of this cytokine during the latent phase of infection has been linked to viral persistence in the salivary glands. In order to further define how IL-10 can temper the immune response to CMV infections, this study will utilize the murine cytomegalovirus infection model. The long term objective of this study is to characterize the mechanisms by which IL-10 controls early inflammatory responses to acute murine cytomegalovirus infection. To address this objective, we will evaluate the effects of IL-10 on the cytokine production, cytotoxicity, and proliferation of (1) natural killer cells, which are critical early antiviral responders and (2) CD8 T cells, which respond at 5-7 days post infection and to recurrent, reactivated MCMV. To this end, flow cytometry, ELISA cytokine analyses, and in vivo cytotoxicity assays will be employed to delineate the role of IL-10 in modulating NK and CD8 T cell anti-viral activity. Understanding the critical immuno-modulatory role(s) of IL-10 on the cellular responses to acute murine cytomegalovirus infection will shed light on how the viral persistence is achieved and provides valuable insight for the generation of therapeutic techniques that effectively enhance viral elimination and improve disease outcomes.
| Gaddi, Pamela J; Crane, Meredith J; Kamanaka, Masahito et al. (2012) IL-10 mediated regulation of liver inflammation during acute murine cytomegalovirus infection. PLoS One 7:e42850 |
