Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

作者：Kochan Travis; Singla Anuj; Tosi Joaquin; Kumar Ashok^*

来源：Infection and Immunity, 2012, 80(6): 2076-2088.

DOI：10.1128/IAI.00149-12

Staphylococcus aureus is a leading cause of severe endophthalmitis, which often results in vision loss in some patients. Previously, we showed that Toll-like receptor 2 (TLR2) ligand pretreatment prevented the development of staphylococcal endophthalmitis in mice and suggested that microglia might be involved in this protective effect (Kumar A, Singh CN, Glybina IV, Mahmoud TH, Yu FS. J. Infect. Dis. 201:255-263,2010). The aim of the present study was to understand how microglial innate response is modulated by TLR2 ligand pretreatment. Here, we demonstrate that S. aureus infection increased the CD11b(+) CD45(+) microglial/macrophage population in the C57BL/6 mouse retina. Using cultured primary retinal microglia and a murine microglial cell line (BV-2), we found that these cells express TLR2 and that its expression is increased upon stimulation with bacteria or an exclusive TLR2 ligand, Pam3Cys. Furthermore, challenge of primary retinal microglia with S. aureus and its cell wall components peptidoglycan (PGN) and lipoteichoic acid (LTA) induced the secretion of proinflammatory mediators (tumor necrosis factor alpha [TNF-alpha] and MIP-2). This innate response was attenuated by a function-blocking anti-TLR2 antibody or by small interfering RNA (siRNA) knockdown of TLR2. In order to assess the modulation of the innate response, microglia were pretreated with a low dose (0.1 or 1 mu g/ml) of Pam3Cys and then challenged with live S. aureus. Our data showed that S. aureus-induced production of proinflammatory mediators is dramatically reduced in pretreated microglia. Importantly, microglia pretreated with the TLR2 agonist phagocytosed significantly more bacteria than unstimulated cells. Together, our data suggest that TLR2 plays an important role in retinal microglial innate response to S. aureus, and its sensitization inhibits inflammatory response while enhancing phagocytic activity.

• 出版日期2012-6