Abstract
Mycobacterium tuberculosis (MTB) infection is characterized by granulomatous lung lesions and systemic inflammatory responses during active disease. Inflammasome activation is involved in regulation of inflammation. Inflammasomes are multiprotein complexes serving a platform for activation of caspase-1, which cleaves the proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18 into their active forms. These cytokines play an essential role in MTB control. MTB infection triggers activation of the nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes in vitro, but only AIM2 and apoptosis-associated speck-like protein containing a caspase-activation recruitment domain (ASC), rather than NLRP3 or caspase-1, favor host survival and restriction of mycobacterial replication in vivo. Interferons (IFNs) inhibits MTB-induced inflammasome activation and IL-1 signaling. In this review, we focus on activation and regulation of the NLRP3 and AIM2 inflammasomes after exposure to MTB, as well as the effect of inflammasome activation on host defense against the infection.
Highlights
Despite the development of chemotherapy and vaccine programs, tuberculosis (TB) continues to lead to increasing death tolls and poses a serious threat to global public health [1]
Its activation requires two signals: signal I contributes to upregulation of IL-1β and NLRP3 in an nuclear factor-κB (NF-κB)-dependent manner, which is called priming, and signal II induces activation of the NLRP3 inflammasome characterized by maturation of IL-1β and caspase-1 [50]
The results indicates that TIRAP C539T is associated with decreased risk for pulmonary tuberculosis (PTB), especially in Europe [143]
Summary
Despite the development of chemotherapy and vaccine programs, tuberculosis (TB) continues to lead to increasing death tolls and poses a serious threat to global public health [1]. One-third of the world’s population is infected with MTB, the main causative agent of TB, and 5-10% of the population develops active TB [2]. IL-1β and IL-18, members of IL-1 family, are potent proinflammatory cytokines [4,5,6] They play a critical role in host defense against MTB infection. Mice deficient in IL-1β or IL-1 receptor type I (IL-1R1) have been shown to be highly susceptible to infection with MTB, as reflected by decreased survival time, increased bacterial burden in lungs and bronchoalveolar lavage fluid (BALF) and extensive pulmonary necrosis [7,8]. Caspase-1 activation is caused by assembly of inflammasome, which is a multiprotein platform for processing and secretion of proinflammatory cytokines as well as initiation of pyroptosis [19]. We discuss the interaction of MTB with inflammasomes and the roles in host defense against the bacteria
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