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MBio. 2016 Jan 12;7(1):e01589-15. doi: 10.1128/mBio.01589-15.

Postprimary Tuberculosis and Macrophage Necrosis: Is There a Big ConNECtion?

Author information

1
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.
2
Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, USA kwwong@gmail.com jacobsw@hhmi.org.

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.

PMID:
26758178
PMCID:
PMC4724999
DOI:
10.1128/mBio.01589-15
[Indexed for MEDLINE]
Free PMC Article

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