Murine {gamma}-Herpesvirus 68 Induces Severe Lung Inflammation in IL-27-Deficient Mice with Liver Dysfunction Preventable by Oral Neomycin [INFECTIOUS DISEASE AND HOST RESPONSE]

IL-27 is an immunoregulatory cytokine consisting of p28 and EBI3. Its receptor also has two subunits, WSX1 and gp130. Although IL-27 promotes Th1 differentiation in naive T cells, it also induces IL-10 expression in effector Th1 cells to curtail excessive immune responses. By using p28-deficient mice and WSX1-deficient mice (collectively called IL-27–deficient mice), we examined the role of IL-27 in primary infection by murine -herpesvirus 68 (MHV68), a murine model of EBV. Upon airway infection with MHV68, IL-27–deficient mice had more aggravated lung inflammation than wild-type mice, although MHV68 infection per se was better controlled in IL-27–deficient mice. Although epithelial cells and alveolar macrophages were primarily infected by MHV68, interstitial macrophages and dendritic cells were the major producers of IL-27. The lung inflammation of IL-27–deficient mice was characterized by more IFN-–producing CD8⁺ T cells and fewer IL-10–producing CD8⁺ T cells than that of wild-type mice. An infectious mononucleosis–like disease was also aggravated in IL-27–deficient mice, with prominent splenomegaly and severe hepatitis. Infiltration of IFN-–producing effector cells and upregulation of the CXCR3 ligand chemokines CXCL9, CXCL10, and CXCL11 were noted in the liver of MHV68-infected mice. Oral neomycin effectively ameliorated hepatitis, with decreased production of these chemokines in the liver, suggesting that the intestinal microbiota plays a role in liver inflammation through upregulation of these chemokines. Collectively, IL-27 is essential for the generation of IL-10–producing effector cells in primary infection by MHV68. Our findings may also provide new insight into the mechanism of hepatitis associated with infectious mononucleosis.

from The Journal of Immunology current issue https://ift.tt/2GKCZPP