Abstract
Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN. M. tuberculosis interaction with any of these receptors activates multiple signaling pathways among which the protein kinase C, the MAPK, and the NFκB pathways have been widely studied. These pathways have been implicated in macrophage invasion, M. tuberculosis survival, and impaired immune response, thus promoting a successful infection and disease. Interestingly, the Wnt signaling pathway, classically regarded as a pathway involved in the control of cell proliferation, migration, and differentiation in embryonic development, has recently been involved in immunoregulatory mechanisms in infectious and inflammatory diseases, such as TB, sepsis, psoriasis, rheumatoid arthritis, and atherosclerosis. In this review, we present the current knowledge supporting a role for the Wnt signaling pathway during macrophage infection by M. tuberculosis and the regulation of the immune response against M. tuberculosis. Understanding the cross talk between different signaling pathways activated by M. tuberculosis will impact on the search for new therapeutic targets to fuel the rational design of drugs aimed to restore the immunological response against M. tuberculosis.
Highlights
Mycobacterium tuberculosis (M. tuberculosis) is the cause of human tuberculosis (TB), which is regarded as one of the most harmful pathogen, just behind HIV, that is responsible for more deaths than any other microorganism
These results suggest that at early stages of the infection, Wnt3 prevents the dissemination of infectious mycobacteria by promoting apoptosis and reducing necrosis of infected macrophages
The pathway analysis of the potential miR150 targets indicates that this mRNA might negatively regulate both the canonical and non-canonical Wnt pathways (Figure 9). These results suggest that the upregulation of miR485 and the negative regulation of miR150 levels are key events triggered by Beijing M. tuberculosis clinical strains to sustain the activation of the canonical Wnt pathway
Summary
M. tuberculosis interaction with any of these receptors activates multiple signaling pathways among which the protein kinase C, the MAPK, and the NFκB pathways have been widely studied. These pathways have been implicated in macrophage invasion, M. tuberculosis survival, and impaired immune response, promoting a successful infection and disease. The Wnt signaling pathway, classically regarded as a pathway involved in the control of cell proliferation, migration, and differentiation in embryonic development, has recently been involved in immunoregulatory mechanisms in infectious and inflammatory diseases, such as TB, sepsis, psoriasis, rheumatoid arthritis, and atherosclerosis. We present the current knowledge supporting a role for the Wnt signaling pathway during macrophage infection by M. tuberculosis and the regulation of the immune response against M. tuberculosis.
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