CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection

Abstract

The role of CXCL9 and CXCL10 in the ocular immune response to herpes simplex virus type 1 (HSV-1) infection was investigated using mice deficient in either CXCL9 or CXCL10. CXCL10 but not CXCL9 deficient mice showed an increase in sensitivity to ocular virus infection as measured by an elevation in virus titer recovered in the tear film and corneal tissue. The increase in virus was associated with an increase in the expression of the chemokine CCL2 but no significant change in the infiltration of CD4 + T cells or NK cells into the corneal stroma. In contrast, a significant reduction in CD4 + T cell infiltration into the cornea was found in CXCL9 deficient mice following HSV-1 infection consistent with the absence of CXCL9 expression and reduction in expression of other chemokines including CCL3, CCL5, CXCL1, and CXCL10. Collectively, the results suggest a nonredundant role for CXCL9 and CXCL10 in response to ocular HSV-1 infection in terms of controlling virus replication and recruitment of CD4 + T cells into the cornea.

CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease

“…The preferential contribution of one CXCR3 ligand to disease pathology has been seen in other inflammatory models of disease, such as CXCL10 in mouse hepatitis virus and Dengue virus encephalitis 29,30 and CXCL9 in herpes simplex virus-1 ocular infection and cytomegalovirus infection. 31,32 Regardless of the exact mechanisms, our findings indicate that selective blockade of CXCL9 and CXCR3 is a potential therapeutic strategy to combat immune-mediated renal diseases.…”

CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8 + T EM and CD8 + T RM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease

“…Results from many mouse models of herpesvirus infection and immunity have yielded tremendous insights into the protective and immunopathological mechanisms during primary acute infection (46)(47)(48)(49)(50)(51)(52). However, the extrapolation of results from mouse primary herpetic disease to human recurrent herpetic diseases, such as recurrent herpetic stromal keratitis (rHSK), is yet to be proven.…”

Significant Association between Serum Monokine Induced by Gamma Interferon and Carotid Intima Media Thickness

“…The preferential contribution of a single CXCR3 chemokine to disease pathology has been reported in other inflammatory models, such as IP-10 in mouse models of hepatitis virus or dengue virus infection 26,27) . MIG has been shown to independently contribute to the pathological response to herpes simplex virus type 1 or cytomegalovirus infection and also in human immunemediated kidney diseases [28][29][30] . Further studies regarding the precise biological role of MIG in the pathogenesis of atherosclerosis are therefore needed.…”