Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation

被引：8

作者：

Chowdhury, Chanchal Sur ^{[1
]}

Kinsella, Rachel L. ^{[1
]}

McNehlan, Michael E. ^{[1
]}

Naik, Sumanta K. ^{[1
]}

Lane, Daniel S. ^{[2
]}

Talukdar, Priyanka ^{[2
]}

Smirnov, Asya ^{[1
]}

Dubey, Neha ^{[1
]}

Rankin, Ananda N. ^{[1
]}

McKee, Samuel R. ^{[1
]}

Woodson, Reilly ^{[1
]}

Hii, Abigail ^{[1
,3
]}

Chavez, Sthefany M. ^{[1
]}

Kreamalmeyer, Darren ^{[1
]}

Beatty, Wandy ^{[1
]}

Mattila, Joshua T. ^{[2
]}

Stallings, Christina L. ^{[1
]}

机构：

[1] Washington Univ, Ctr Womens Infect Dis Res, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[2] Univ Pittsburgh, Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA

[3] Univ Coll Dublin, UCD Sch Med, Dublin, Ireland

来源：

CELL HOST & MICROBE | 2024年 / 32卷 / 12期

关键词：

NEUTROPHIL EXTRACELLULAR TRAPS; CHROMATIN DECONDENSATION; INNATE IMMUNITY; INFECTION; MYELOPEROXIDASE; SUSCEPTIBILITY; ACTIVATION; CONTRIBUTE; BACTERIAL; NECROSIS;

D O I：

10.1016/j.chom.2024.11.008

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Neutrophils are the most abundant cell type in the airways of tuberculosis patients. Mycobacterium tuberculosis (Mtb) infection induces the release of neutrophil extracellular traps (NETs); however, the molecular regulation and impact of NET release on Mtb pathogenesis are unknown. We find that during Mtb infection in neutrophils, PAD4 citrullinates histones to decondense chromatin that gets released as NETs in a manner that can maintain neutrophil viability and promote Mtb replication. Type I interferon promotes the formation of chromatin-containing vesicles that allow NET release without compromising plasma membrane integrity. Analysis of nonhuman primate granulomas supports a model where neutrophils are exposed to type I interferon from macrophages as they migrate into the granuloma, thereby enabling the release of NETs associated with necrosis and caseation. Our data reveal NET release as a promising target to inhibit Mtb pathogenesis.

引用

页码：2092 / 2111.e7

页数：28

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