Purchase this article with an account.
Ashok Kumar, Pawan Kumar Singh, Deepa Talreja; Critical role of TLR2 and MyD88 signaling in controlling bacterial burden in mouse model of S. aureus endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):168. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Recent studies have implicated an important role of Toll like receptor 2 (TLR 2) in providing retinal innate defense in bacterial endophthalmitis. TLR2 signals via MyD88-dependent pathway to initiate inflammatory cascades, which are critical for recruitment of immune cells, which in turn limit bacterial growth. In this study we investigated the role of TLR2 and MyD88 in pathogen clearance using knockout mice.
Endophthalmitis was induced in wild-type (WT), TLR2-/- and MyD88-/- mice by intravitreal injections of S aureus. Eyes were examined for corneal opacity and vitreous haze 1, 2, and 3 days post infection (dpi). Bacterial burden was determined by colony forming units (CFUs) of eye lysates. Flowcytometry was used for PMN infiltration and cytometric bead array (CBA) detection of inflammatory mediators. Eyes were also fixed and embedded in paraffin for histological analysis.
Both TLR2-/- and MyD88-/- exhibited increased bacterial burden with MyD88-/- being the highest as compared to WT mice. Similar trend was observed for clinical scores, with MyD88-/- mice showing increased and TLR2-/- showing intermediate clinical scores. At 3 dpi, eyes were completely damaged in MyD88-/- mice as supported by histological data. At early stages the PMN infiltration and levels of inflammatory cytokines was less in TLR2-/- and MyD88-/- mice. However, their levels dramatically increased at later stages (3 dpi) of infection.
Our data suggests that TLR2 and MyD88 deficiencies results in increased bacterial proliferation in the eye leading to severe intraocular inflammation and retinal damage during endophthalmitis.
This PDF is available to Subscribers Only