Tuberculosis (TB), caused by the ancient pathogen Mycobacterium tuberculosis (M.tb), is a highly infectious disease. Alveolar macrophages, as a residing niche for M.tb, exert immuno-modulatory and microbicidal effects. In the macrophage, M.tb can adapt to the environment, to achieve the goal of longer survival and dissemination of the bacteria in the surrounding environment. A better understanding of the host-mycobacteria interactions is necessary for the discovery of new immunotherapeutic targets and the establishment of effective host-direct therapies (HDT). Elongated mitochondria and enhanced mitochondrial interconnectivity were found in M.tb-infected macrophages. These changes of dynamics were achieved by increased expression of mitofusin 1 (MFN1) and accompanied by enhanced mitochondrial oxidative phosphorylation (OXPHOS) and ATP production, which are required for the autophagy process and suppression of intracellular bacterial growth. A comprehensive lipid mediators (LM) profile of M.tb-conditioned medium (MTB-CM)-stimulated M1-macrophages was analyzed by UPLC-MS/MS. Decreased expression of cycloxygenase 2 (COX-2) and prostaglandin E2 (PGE2) were proposed as the reasons for the resolving and potential microbicidal activity of sulfasalazine (SASP). As one of the highly expressed prostaglandins (PGs) in MTB-CM-stimulated M1-macrophages, prostaglandin J2 (PGJ2) was found to suppress pro-inflammatory cytokines expression and inhibit COX-2 expression via a negative feedback loop. PGJ2 also decreased the mycobacterial phagocytosis ability of macrophages and increased intracellular bacterial survival rate. Taken together, the findings presented in this thesis provide new insights into how M.tb modulates macrophage reactions within the immune system. The interactions between M.tb and host including mitochondrial dynamics regulation and LM biosynthesis might be promising targets for the development of HDT strategies against TB.