Type I IFN-mediated NET Release Promotes Mycobacterium Tuberculosis Replication and is Associated with Granuloma Caseation

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2024 Dec 5

PMID 39637864

Authors

Chanchal Sur Chowdhury

Rachel L Kinsella

Michael E McNehlan

Sumanta K Naik

Daniel S Lane

Priyanka Talukdar

Asya Smirnov

Neha Dubey

Ananda N Rankin

Samuel R McKee

Reilly Woodson

Abigail Hii

Sthefany M Chavez

Darren Kreamalmeyer

Wandy Beatty

Joshua T Mattila

Christina L Stallings

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Spatial transcriptomic analysis of HIV and tuberculosis coinfection in a humanized mouse model reveals specific transcription patterns, immune responses and early morphological alteration signaling.

Adduri S, Bohorquez J, Adejare O, Rincon D, Tucker T, Konduru N bioRxiv. 2025; .

PMID: 39975088 PMC: 11838271. DOI: 10.1101/2025.01.29.635571.

References

Li P, Li M, Lindberg M, Kennett M, Xiong N, Wang Y . PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010; 207(9):1853-62. PMC: 2931169. DOI: 10.1084/jem.20100239. View

Fuchs T, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers Jr D . Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010; 107(36):15880-5. PMC: 2936604. DOI: 10.1073/pnas.1005743107. View

Smith C, Baker R, Proulx M, Mishra B, Long J, Park S . Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice. Elife. 2022; 11. PMC: 8846590. DOI: 10.7554/eLife.74419. View

Parker H, Dragunow M, Hampton M, Kettle A, Winterbourn C . Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus. J Leukoc Biol. 2012; 92(4):841-9. DOI: 10.1189/jlb.1211601. View

Subbian S, Tsenova L, OBrien P, Yang G, Koo M, Peixoto B . Phosphodiesterase-4 inhibition combined with isoniazid treatment of rabbits with pulmonary tuberculosis reduces macrophage activation and lung pathology. Am J Pathol. 2011; 179(1):289-301. PMC: 3123788. DOI: 10.1016/j.ajpath.2011.03.039. View

Narasaraju T, Yang E, Perumal Samy R, Ng H, Poh W, Liew A . Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011; 179(1):199-210. PMC: 3123873. DOI: 10.1016/j.ajpath.2011.03.013. View

Braian C, Hogea V, Stendahl O . Mycobacterium tuberculosis- induced neutrophil extracellular traps activate human macrophages. J Innate Immun. 2013; 5(6):591-602. PMC: 6741595. DOI: 10.1159/000348676. View

Nair S, Huynh J, Lampropoulou V, Loginicheva E, Esaulova E, Gounder A . expression in myeloid cells prevents immunopathology during infection. J Exp Med. 2018; 215(4):1035-1045. PMC: 5881474. DOI: 10.1084/jem.20180118. View

Tatsiy O, McDonald P . Physiological Stimuli Induce PAD4-Dependent, ROS-Independent NETosis, With Early and Late Events Controlled by Discrete Signaling Pathways. Front Immunol. 2018; 9:2036. PMC: 6153332. DOI: 10.3389/fimmu.2018.02036. View

10.

Hoff D, Ryan G, Driver E, Ssemakulu C, De Groote M, Basaraba R . Location of intra- and extracellular M. tuberculosis populations in lungs of mice and guinea pigs during disease progression and after drug treatment. PLoS One. 2011; 6(3):e17550. PMC: 3061964. DOI: 10.1371/journal.pone.0017550. View

11.

Brahmbhatt S, Black G, Carroll N, Beyers N, Salker F, Kidd M . Immune markers measured before treatment predict outcome of intensive phase tuberculosis therapy. Clin Exp Immunol. 2006; 146(2):243-52. PMC: 1942062. DOI: 10.1111/j.1365-2249.2006.03211.x. View

12.

Manca C, Tsenova L, Freeman S, Barczak A, Tovey M, Murray P . Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway. J Interferon Cytokine Res. 2005; 25(11):694-701. DOI: 10.1089/jir.2005.25.694. View

13.

Sivanandham R, Brocca-Cofano E, Krampe N, Falwell E, Venkatraman S, Ribeiro R . Neutrophil extracellular trap production contributes to pathogenesis in SIV-infected nonhuman primates. J Clin Invest. 2018; 128(11):5178-5183. PMC: 6205390. DOI: 10.1172/JCI99420. View

14.

Thiam H, Wong S, Qiu R, Kittisopikul M, Vahabikashi A, Goldman A . NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture. Proc Natl Acad Sci U S A. 2020; 117(13):7326-7337. PMC: 7132277. DOI: 10.1073/pnas.1909546117. View

15.

Neeli I, Khan S, Radic M . Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol. 2008; 180(3):1895-902. DOI: 10.4049/jimmunol.180.3.1895. View

16.

Garcia-Romo G, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z . Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med. 2011; 3(73):73ra20. PMC: 3143837. DOI: 10.1126/scitranslmed.3001201. View

17.

Lin P, Coleman T, Carney J, Lopresti B, Tomko J, Fillmore D . Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis Chemotherapy Regimens. Antimicrob Agents Chemother. 2013; 57(9):4237-4244. PMC: 3754323. DOI: 10.1128/AAC.00277-13. View

18.

Ramos-Kichik V, Mondragon-Flores R, Mondragon-Castelan M, Gonzalez-Pozos S, Muniz-Hernandez S, Rojas-Espinosa O . Neutrophil extracellular traps are induced by Mycobacterium tuberculosis. Tuberculosis (Edinb). 2008; 89(1):29-37. DOI: 10.1016/j.tube.2008.09.009. View

19.

Keller C, Hoffmann R, Lang R, Brandau S, Hermann C, Ehlers S . Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes. Infect Immun. 2006; 74(7):4295-309. PMC: 1489748. DOI: 10.1128/IAI.00057-06. View

20.

Lee A, Laurent P, Nathan C, Barrat F . Neutrophil-plasmacytoid dendritic cell interaction leads to production of type I IFN in response to Mycobacterium tuberculosis. Eur J Immunol. 2023; 54(3):e2350666. DOI: 10.1002/eji.202350666. View