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

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

doi:10.1016/j.chom.2024.11.008

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

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

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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.

Original language	English
Pages (from-to)	2092-2111.e7
Journal	Cell Host and Microbe
Volume	32
Issue number	12
DOIs	https://doi.org/10.1016/j.chom.2024.11.008
State	Published - Dec 11 2024

Keywords

PAD4
bacterial pathogenesis
granuloma
histone citrullination
mycobacterium
necrosis
neutrophil extracellular traps
neutrophils
tuberculosis
type I interferon

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10.1016/j.chom.2024.11.008

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Chowdhury, C. S., Kinsella, R. L., McNehlan, M. E., Naik, S. K., Lane, D. S., Talukdar, P., Smirnov, A., Dubey, N., Rankin, A. N., McKee, S. R., Woodson, R., Hii, A., Chavez, S. M., Kreamalmeyer, D., Beatty, W., Mattila, J. T., & Stallings, C. L. (2024). Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation. Cell Host and Microbe, 32(12), 2092-2111.e7. https://doi.org/10.1016/j.chom.2024.11.008

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

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.",

keywords = "PAD4, bacterial pathogenesis, granuloma, histone citrullination, mycobacterium, necrosis, neutrophil extracellular traps, neutrophils, tuberculosis, type I interferon",

author = "Chowdhury, {Chanchal Sur} and Kinsella, {Rachel L.} and McNehlan, {Michael E.} and Naik, {Sumanta K.} and Lane, {Daniel S.} and Priyanka Talukdar and Asya Smirnov and Neha Dubey and Rankin, {Ananda N.} and McKee, {Samuel R.} and Reilly Woodson and Abigail Hii and Chavez, {Sthefany M.} and Darren Kreamalmeyer and Wandy Beatty and Mattila, {Joshua T.} and Stallings, {Christina L.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = dec,

day = "11",

doi = "10.1016/j.chom.2024.11.008",

language = "English",

volume = "32",

pages = "2092--2111.e7",

journal = "Cell Host and Microbe",

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Chowdhury, CS, Kinsella, RL, McNehlan, ME, Naik, SK, Lane, DS, Talukdar, P, Smirnov, A, Dubey, N, Rankin, AN, McKee, SR, Woodson, R, Hii, A, Chavez, SM, Kreamalmeyer, D, Beatty, W, Mattila, JT & Stallings, CL 2024, 'Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation', Cell Host and Microbe, vol. 32, no. 12, pp. 2092-2111.e7. https://doi.org/10.1016/j.chom.2024.11.008

TY - JOUR

T1 - Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation

AU - Chowdhury, Chanchal Sur

AU - Kinsella, Rachel L.

AU - McNehlan, Michael E.

AU - Naik, Sumanta K.

AU - Lane, Daniel S.

AU - Talukdar, Priyanka

AU - Smirnov, Asya

AU - Dubey, Neha

AU - Rankin, Ananda N.

AU - McKee, Samuel R.

AU - Woodson, Reilly

AU - Hii, Abigail

AU - Chavez, Sthefany M.

AU - Kreamalmeyer, Darren

AU - Beatty, Wandy

AU - Mattila, Joshua T.

AU - Stallings, Christina L.

PY - 2024/12/11

Y1 - 2024/12/11

N2 - 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.

AB - 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.

KW - PAD4

KW - bacterial pathogenesis

KW - granuloma

KW - histone citrullination

KW - mycobacterium

KW - necrosis

KW - neutrophil extracellular traps

KW - neutrophils

KW - tuberculosis

KW - type I interferon

UR - http://www.scopus.com/inward/record.url?scp=85211208338&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2024.11.008

DO - 10.1016/j.chom.2024.11.008

M3 - Article

C2 - 39637864

AN - SCOPUS:85211208338

SN - 1931-3128

VL - 32

SP - 2092-2111.e7

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 12

ER -

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

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Keywords

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