ROLE OF ANNEXIN-1 IN PATHOGEN RECOGNITION AND IMMUNE RESPONSE

Abstract

Annexin-1 is a glucocorticoid- inducible anti-inflammatory protein. TLR stimulation induces pro-inflammatory response based on pathogen specific recognition and activation by TLR. It mounts either an anti-bacterial / anti- fungal response (MyD88 dependent) or anti-viral (TRIF dependent) response. This study looks at pathogen specific TLR agonist stimulated activation and immune response in ANXA1 KO macrophages. When stimulated with TLR agonists poly (I:C) and LPS, ANXA1 KO macrophages show attenuated MyD88 dependent IL-12 production and TRIF dependent IP-10 production. This study also investigated nuclear localization of IRF-3 and NF-¿B p65 after stimulation with TLR agonists, and was found to be impaired in ANXA1 KO macrophages. Endogenous NF-¿B inhibitor PPAR-¿ and macrophage polarization was investigated to determine the source of impairment. Annexin-1 regulates M1 polarization through NF-¿B and IRF-3, but not STAT-1 activation. Moreover, annexin-1 is capable of suppressing M2 polarization. These results show that annexin-1 regulates both TLR signalling and macrophage polarization.