title: Postprimary Tuberculosis and Macrophage Necrosis: Is There a Big ConNECtion?
abstract: Adult or postprimary tuberculosis (TB) accounts for most TB cases. Its hallmark is pulmonary cavitation, which occurs as a result of necrosis in the lung in individuals with tuberculous pneumonia. Postprimary TB has previously been known to be associated with vascular thrombosis and delayed-type hypersensitivity, but their roles in pulmonary cavitation are unclear. A necrosis-associated extracellular cluster (NEC) refers to a cluster of drug-tolerant Mycobacterium tuberculosis attached to lysed host materials and is proposed to contribute to granulomatous TB. Here we suggest that NECs, perhaps due to big size, produce a distinct host response leading to postprimary TB. We propose that vascular thrombosis and pneumonia arise from NEC and that these processes are promoted by inflammatory cytokines produced from cell-mediated delayed-type hypersensitivity, such as interleukin-17 and gamma interferon, eventually triggering necrosis in the lung and causing cavitation. According to this view, targeting NEC represents a necessary strategy to control adult TB.
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China kwwong@gmail.com jacobsw@hhmi.org.
authors.forename: Ka-Wing
authors.identifier: http://orcid.org/0000-0001-8356-5880
authors.initials: KW
authors.lastname: Wong
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, USA kwwong@gmail.com jacobsw@hhmi.org.
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D008264:Macrophages / Q000382:microbiology* / Q000502:physiology*; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D009336:Necrosis; D014397:Tuberculosis, Pulmonary / Q000473:pathology*