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Depletion of MCP‐1 increases development of herpetic stromal keratitis by innate immune modulation
Author(s) -
Kim Bumseok,
Sarangi Pranita P.,
Lee Yunsang,
Deshpande Kaistha Shilpa,
Lee Sujin,
Rouse Barry T.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0406295
Subject(s) - chemokine , biology , cornea , immunology , stromal cell , ccr2 , ccl2 , chemotaxis , immune system , inflammation , innate immune system , monocyte , keratitis , infiltration (hvac) , cancer research , chemokine receptor , receptor , biochemistry , genetics , physics , neuroscience , thermodynamics
Chemokines are important chemoattractant inflammatory molecules, but their interdependent network in disease pathogenesis remains unclear. Studies in mouse models have shown that herpetic stromal keratitis (SK) is produced by the consequence of a tissue‐destructive immunoinflammatory reaction involving herpes simplex virus type 1 (HSV) infection. Here we found that ocular HSV infection leads to increased expression of monocyte chemoattractant protein‐1 (MCP‐1), one of the major chemoattractants for immune cells that express CCR2, in the SK cornea. However, MCP‐1 is unlikely to be a chemoattractant for infiltrating Gr‐1 + , CD11b + cells in SK, as these cells are found to be CCR2 negative. Nevertheless, infection of MCP‐1 −/− mice resulted in more severe SK lesion severity compared with WT mice ( P <0.01). We demonstrated that the loss of MCP‐1 in the SK cornea caused a significant overexpression of macrophage inflammatory protein‐2 (MIP‐2) ( P <0.01) on days 2 and 4 postinfection and increased infiltration of inflammatory cells (Gr‐1‐high and CD11b + ) expressing CXCR2, a receptor for MIP‐2, into the cornea. Subsequently, increased infiltration of inflammatory cells accelerated by MIP‐2 overexpression might result in the high production of inflammatory molecules, including vascular endothelial growth factor (VEGF) and IL‐1β in SK, as well as CpG oligodeoxynucleotide (ODN)‐implanted eyes of MCP‐1 −/− mice. These results indicate that MCP‐1 in the SK cornea might regulate the expression of other chemokines, as well as the infiltration of inflammatory cells and control development of SK.