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Y. Sun, C. Kalsow, E. Pearlman; Corneal Inflammation Induced by Killed Staphylococcus Aureus is Dependent on Toll–Like Receptor (TLR)2 and MyD88 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4370.
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© ARVO (1962-2015); The Authors (2016-present)
Toll–like receptors (TLR) in the corneal epithelium represent a first line of defense in microbial keratitis. To determine the role of TLRs and the common adaptor molecule MyD88 in the early host response to S. aureus, we examined the TLR response to killed S.aureus in TLR reporter cells, in human corneal epithelial cells, and in a murine model of keratitis.
The corneal epithelium of C57BL/6, TLR2–/–, TLR4–/–, TLR9–/– and MyD88–/–mice was abraded and exposed to heat or UV–killed S. aureus strain 8325 and other clinical isolates. Corneal thickness and haze of inflammation was measured in vivo by confocal microscopy, and neutrophil infiltration to the corneal stroma was quantitated by immunohistochemistry. Cytokine response (IL–6 and IL–8) of primary human corneal epithelial (HCE) cells and HCE cells lines activated by killed S. aureus in the presence or absence of anti–TLR2 antibody and the response of TLR2–, TLR3–, and TLR4– expressing reporter human embryonic kidney (HEK) cells stimulated with killed S. aureus were measured by ELISA.
S. aureus induced corneal haze, increased thickness and neutrophil infiltration in C57BL/6, TLR4–/– and TLR9–/– mice. In marked contrast, these markers of corneal inflammation did not develop in TLR2–/– or MyD88–/– mice. Consistent with in vivo observations, activation of S. aureus– induced HCE cells was blocked by specific TLR2 antibody, and HEK/TLR2–expressing cells responded to S. aureus but HEK/TLR3 or HEK/TLR4–expressing cells did not respond.
TLR2 is the major receptor for heat or UV killed S. aureus in the corneal epithelium, and stimulation of this receptor in vivo induces MyD88–dependent corneal inflammation. These findings reveal an essential pathway in development of the early host response to S.aureus.
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