DNA from virulent M. tuberculosis induces TNF-α production and autophagy in M1 polarized macrophages

• Published in: Microbial pathogenesis Vol. 132; pp. 166 - 177
• Main Authors: Ruiz, Andy, Guzmán-Beltrán, Silvia, Carreto-Binaghi, Laura E., Gonzalez, Yolanda, Juárez, Esmeralda
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2019
• Subjects: Autophagy; DNA; DNA, Bacterial - genetics; DNA, Bacterial - isolation & purification; Humans; Immunity, Innate; Macrophages; Macrophages - metabolism; Monocytes; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Phenotype; TLR-9; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Mycobacterium tuberculosis; Macrophages; TLR-9; Autophagy; DNA
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2019.04.041

The macrophage innate immune response is outlined through recognition of the components of Mycobacterium tuberculosis. DNA of M. tuberculosis (MtbDNA) is recognized by macrophages, but the implications of this recognition are poorly characterized. Stimulation of murine macrophages with MtbDNA induces autophagy, a process that promotes elimination of intracellular pathogens. However, it remains unknown whether this or other phenomena also occur in human cells. In this work, we studied the innate response profiles of human macrophages after stimulation with DNA from virulent M. tuberculosis H37Rv. Human monocyte-derived macrophages were polarized into M1 and M2 phenotypes and stimulated with MtbDNA. The plasma membrane markers of the phenotype, production of TNF-α, and induction of autophagy were evaluated. Our results indicate that MtbDNA induced phenotypical changes, the significant production of TNF-α, and autophagy confirmed by the augmented expression of immunity related GTPase M (IRGM) and autophagy related ATG16L1 genes in M1 macrophages, whereas M2 macrophages exhibited limited responses. In addition, MtbDNA activation was TLR-9-dependent. Although TLR-9 expression was similar between M1 and M2 macrophages, only M1 macrophages were fully responsive to MtbDNA. In conclusion, MtbDNA recognition enhanced the antimicrobial mechanisms of M1 macrophages. [Display omitted] •TLR-9 recognizes M. tuberculosis DNA and induces TNF-α production.•Cell-free M. tuberculosis DNA is recognized by M1 macrophages.•M1 macrophages initiate autophagy after recognizing M. tuberculosis DNA.