<p>Nontuberculous mycobacteria (NTM) refers to all mycobacteria except Mycobacterium tuberculosis (<i>Mtb</i>) and <i>Mycobacterium leprae</i> (<i>M. leprae</i>). In recent years, its incidence and prevalence have been increasing worldwide, which has attracted the attention of medical and scientific research circles. We determined the immune mechanism of <i>Mycobacterium neoaurum</i> (<i>M. neoaurum</i>) and Bacillus Calmette-Guérin (BCG) by studying the association between <i>M. neoaurum</i> and BCG infection and the release of IL-1β and IL-18, the assembly of inflammatory body, and pyroptosis. Macrophages were infected with <i>M. neoaurum</i> and BCG. The secretion of IL-1β and IL-18 was detected by ELISA, and the gene expression and protein expression of IL-1β, IL-18, NLRP3, AIM2, ASC, caspase-1 and GSDMD were detected by RT-PCR and Western Blot. NLRP3 and AIM2 inflammasome assembly was induced by <i>M. neoaurum</i> and BCG infection in mouse macrophages, which activated caspase-1 and induced the maturation and secretion of IL-1β and IL-18. The secretion of IL-1β and IL-18 were regulated by ATP-dependent K⁺ channel. At the same time, <i>M. neoaurum</i> and BCG infection can also induce pyroptosis. This study was limited by the lack of in vivo mouse experiments. The research findings suggest that the activation of NLRP3 and AIM2 inflammasomes may be involved in the host defense against M. neoaurum and BCG, and the process of pyroptosis may also be related to this.</p>