Mycobacterium tuberculosis remains an important cause of morbidity and mortality worldwide. Macrophages (Mφs) represent first line to defense against pathgens. Pattern recognition receptors (PRRs) expressed on Mφs detect pathogen-associated molecular patterns (PAMPs) of pathogens to activate immune responses. Recent reports have highlighted the importance of ITAM-coupled receptors (ITAMRs) including C-type lectin receptors in the recognition of PAMPs to regulate immune responses. Mycobacteria paradoxically live in macrophages. Thus the regulation of immune responses are important for mycobacterial infection. In this study, we found that one of ITAMRs TREM2 directly recognized mycobacterial PAMPs, mycolic acid (MA) and MA-containing lipids. Its recognition of non-glycosylated MAs, such MA itself and glycerol monomycolate (GroMM), induced the production of MCP-1 but not TNF-α and any other inflammatory cytokines, as far as we examined. In contrast, Mincle, which is the receptor for Torehalose-di-mycolate (TDM), also recognized another glycosylated MA, GMM but not non-glycosylated MAs. Mincle recognition of these glycosylated MAs induced the production of various cytokines including MCP-1 and TNF-α. The glycosylated but not non-glycosylated MAs also induced nitric oxide (NO) production. Interestingly, TREM2 is found to also ecognize these glycosylated MAs and inhibited these cytokine and NO productions. BCG infection of Trem2--deficient mice accelerated clearance of bacteria comparing to that of WT. These results shows the glycosylated MAs and non-glycosylated MAs differently regulate host immune responses through Mincle and TREM2. Although Mincle recruits macrophages for killing bacteria, TREM2 harness the host immunity to produce only MCP-1 to recruit macrophages lacking bactericidal activity for their propagation.