FIG 1.

Molecular mechanisms leading to IL-1β production in M. tuberculosis-infected cells. The recognition of M. tuberculosis molecular patterns by TLR2/6 or NOD2 induces a series of signaling cascades that culminate in the transcription of the IL-1β mRNA. The glycolytic reprogramming of the infected macrophage also enhances Il1b transcription. Biological activation of IL-1β requires cleavage of pro-IL-1β through canonical or noncanonical mechanisms. Canonical activation consists of the assembly of NLRP3 and AIM2 inflammasomes, which are triggered by the recognition of pathogen-associated molecular patterns/damage associated molecular patterns (PAMPs/DAMPs) and bacterial DNA, respectively, resulting from the export of bacterial products from the phagolysosome. The assembly of the inflammasomes leads to the recruitment of CASP1 by ASC. CASP1 becomes activated and cleaves pro-IL-1β into active IL-1β. Noncanonical activation is much less studied in the context of M. tuberculosis but may be mediated by elastases, matrix metalloproteinases (MMPs), other caspases, and chymases.