Mycobacterium tuberculosis LprE enhances bacterial persistence by inhibiting cathelicidin and autophagy in macrophages

Abstract

Mycobacterium tuberculosis (Mtb) lipoproteins are known to facilitate bacterial survival by manipulating the host immune responses. Here, we have characterized a novel Mtb lipoprotein LprE (LprE_Mtb), and demonstrated its role in mycobacterial survival. LprE_Mtb acts by down-regulating the expression of cathelicidin, Cyp27B1, VDR and p38-MAPK via TLR-2 signaling pathway. Deletion of lprE_Mtb resulted in induction of cathelicidin and decreased survival in the host. Interestingly, LprE_Mtb was also found to inhibit autophagy mechanism to dampen host immune response. Episomal expression of LprE_Mtb in non-pathogenic Mycobacterium smegmatis (Msm) increased bacillary persistence by down-regulating the expression of cathelicidin and autophagy, while deletion of LprE_Mtb orthologue in Msm, had no effect on cathelicidin and autophagy expression. Moreover, LprE_Mtb blocked phago-lysosome fusion by suppressing the expression of EEA1, Rab7 and LAMP-1 endosomal markers by down-regulating IL-12 and IL-22 cytokines. Our results indicate that LprE_Mtb plays an important role in mycobacterial pathogenesis in the context of innate immunity.