We suggest that, in the absence of adaptive immune responses resulting from severe CD4+ T cell depletion caused by HIV-1 infection, or infection with a novel pathogen in people with SARS-CoV-2 infection, innate immune responses against mycobacteria or SARS-CoV-2, respectively, are induced leading to activation of monocytes/macrophages, including NLRP3-inflammasome activation and IL-18 production. The gene discussed is NLRP3; the disease is HIV-1 infection.