The role of Toll‐like receptor 2 in macrophage activation (1125.3)

Abstract

The role of Toll‐Like Receptor 2 (TLR2) in macrophage activation Kyeong Ran Jang1,2, John C. Gensel2, 1APS Undergraduate Summer Research Fellow; 2Spinal Cord and Brain Injury Research Center; Department of Physiology; University of Kentucky Macrophages (MO) are a hallmark of injury and can contribute to pathology or repair. In CNS trauma, MO induces axon dieback. Injecting TLR2 agonist to the site of CNS trauma reduces dieback, with increased MO activation. We hypothesize that TLR2 activation regulates the pathological potential of MO. TLR co‐activation with other stimuli induces a regulatory (M2b) MO phenotype. Through activation of TLR4, M2b MO releases IL10 (anti‐inflammatory cytokine) to help resolve inflammation. Little is known if TLR2 can drive an M2b phenotype. We tested our hypothesis by stimulating bone marrow‐derived and RAW cell MO with zymosan (ZYM). ZYM mimics MO activation at CNS trauma by co‐activation of TLR2 and other stimuli. 4 activation groups were tested: 1) untreated, 2) ZYM, 3) ZYM without TLR2 (DZYM), and 4) PAM2CSK4 (TLR2 agonist). All results are indicative of multiple independent replications. Examining IL10, IL12, CD80, CD86, and CCL1 gene markers after 6hrs of stimulation, ZYM stimulated MO significantly up‐regulated IL10 and CD86 (2 markers of the M2b MO). Notably, neither DZYM nor PAM2CSK4 alone was sufficient to drive M2b activation. There were no significant differences in other markers among groups and results were similar for both cell types. We conclude that TLR2 induces an M2b regulatory phenotype. Identifying TLR2 as target for MO opens new ways for therapeutic strategies to limit the pathological properties of MO.