Murine gammaherpesvirus-68-induced interleukin-10 increases viral burden, but limits virus-induced splenomegaly and leukocytosis.
Based on its genomic sequence and its pathogenesis, murine gammaherpesvirus-68 (gammaHV-68) has been established as a tractable model for the study of viral infections caused by the human gammaherpesviruses, Epstein-Barr virus or human herpesvirus-8. Despite significant advances, the mechanisms responsible for gammaHV-68-induced alterations in the protective host response, and the accompanying virus-induced leukocytosis, are not clear. In the present study, we questioned whether viral infection resulted in endogenous interleukin-10 (IL-10) production that might alter the host response. Infection of C57BL/6 mice resulted in increased IL-10 expression, demonstrating that gammaHV-68 could induce endogenous production of this cytokine. Infected C57BL/6 mice demonstrated the characteristic splenomegaly associated with this viral infection, however, we were surprised to discover that the splenomegaly was greater in syngeneic mice genetically deficient in IL-10 (IL-10-/-). These results strongly suggested that endogenously produced IL-10 might serve to limit leukocytosis in wild-type mice. Quantification of viral burden demonstrated a significant elevation in C57BL/6 versus IL-10-/- mice, with increases in virus being observed in both the macrophage and B-lymphocyte populations. The decreased viral load in syngeneic IL-10-/- mice correlated with an increased expression of endogenous IL-12, suggesting a mechanism of protection that was IL-12 dependent. Taken together, these studies demonstrate a surprising dichotomy for endogenous IL-10 production during gammaHV-68 infection. While the lack of IL-10 results in increased IL-12 expression and a lower viral burden, IL-10-/- mice also experience an increased leukocytosis.
Peacock
J W
JW
Department of Biology, University of North Carolina at Charlotte, NC 28223, USA.
Bost
K L
KL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018142:Gammaherpesvirinae; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D007964:Leukocytosis / Q000276:immunology / Q000821:virology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology / Q000821:virology*; D019562:Viral Load
D016753:Interleukin-10; D018664:Interleukin-12