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D. J. Carr, M. Thapa, T. Wuest; Resident but Not Hematopoietic-Derived Cells Contribute to Production of CXCL10 and Resistance to HSV-1 Infection in the Cornea. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1202.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the relationship between resident versus hematopoietic-derived cell production of CXCL10 and resistance to herpes simplex virus type 1 (HSV-1) following corneal infection.
CXCL10 deficient bone marrow (BM) chimeras were generated by lethal irradiation (6.5 Gy/650 RADS/exposure, 2x over 4 hrs) of congenic (CD45.1) C57BL/6 wild type (WT) mice followed by transfer of 1x106 BM cells from CXCL10 deficient (CXCL10-/-) or WT mice. Following a 12 week period to establish the chimera, WT, WT BM chimeras, and CXCL10-/- BM chimeras, and CXCL10-/- mice were infected with HSV-1 (1,000 plaque forming units/eye) following corneal scarification. At day 7 post infection, mice were exsanguinated and the corneas and trigeminal ganglia (TG) were removed and assayed for viral titer by plaque assay, chemokine (CCL2, CXCL9, and CXCL10) content by ELISA, and infiltration of leukocytes by flow cytometry.
Following HSV-1 infection, CXCL10-/- mouse corneas possessed elevated levels of HSV-1 in comparison to WT or WT BM chimeras. CXCL10-/- BM chimera cornea HSV-1 titers were reduced in comparison to CXCL10-/- mice but elevated in comparison to WT or WT BM mice. By comparison, similar viral titers found in the TG of CXCL10-/- and CXCL10-/- BM chimeric mice were significantly elevated in comparison to levels from WT or WT BM mice. Similar levels of CXCL10 were expressed in the cornea of WT, WT BM chimeras, and CXCL10-/- BM chimeras. Similar levels of chemokines were expressed in the TG of WT, WT BM chimeras, and CXCL10-/- BM chimeras.
The expression of CXCL10 by resident cells within the cornea facilitates virus clearance presumably thru chemoattraction of leukocytes to the infected tissue. In contrast, hematopoietic-derived CXCL10 is necessary for resistance to HSV-1 infection within the TG. The results support the tissue-specific dependence of CXC10 expression on resistance to ocular HSV-1 infection.
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