Neutrophils Exert Protection in the Early Tuberculous Granuloma by Oxidative Killing of Mycobacteria Phagocytosed from Infected Macrophages

Chao-Tsung Yang; C.J Cambier; J. Muse Davis; Christopher J Hall; Philip S Crosier; Lalita Ramakrishnan

doi:10.1016/j.chom.2012.07.009

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Neutrophils Exert Protection in the Early Tuberculous Granuloma by Oxidative Killing of Mycobacteria Phagocytosed from Infected Macrophages

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Neutrophils Exert Protection in the Early Tuberculous Granuloma by Oxidative Killing of Mycobacteria Phagocytosed from Infected Macrophages

Chao-Tsung Yang, C.J Cambier, J. Muse Davis, Christopher J Hall, Philip S Crosier and Lalita Ramakrishnan

Cell host & microbe, Vol.12(3), pp.301-312

09/13/2012

DOI: 10.1016/j.chom.2012.07.009

PMCID: PMC3638950

PMID: 22980327

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Abstract

Neutrophils are typically the first responders in host defense against invading pathogens, which they destroy by both oxidative and nonoxidative mechanisms. However, despite a longstanding recognition of neutrophil presence at disease sites in tuberculosis, their role in defense against mycobacteria is unclear. Here we exploit the genetic tractability and optical transparency of zebrafish to monitor neutrophil behavior and its consequences during infection with Mycobacterium marinum , a natural fish pathogen. In contrast to macrophages, neutrophils do not interact with mycobacteria at initial infection sites. Neutrophils are subsequently recruited to the nascent granuloma in response to signals from dying infected macrophages within the granuloma, which they phagocytose. Some neutrophils then rapidly kill the internalized mycobacteria through NADPH oxidase-dependent mechanisms. Our results provide a mechanistic link to the observed patterns of neutrophils in human tuberculous granulomas and the susceptibility of humans with chronic granulomatous disease to mycobacterial infection.

Details

Title: Subtitle: Neutrophils Exert Protection in the Early Tuberculous Granuloma by Oxidative Killing of Mycobacteria Phagocytosed from Infected Macrophages
Creators: Chao-Tsung Yang - Department of Microbiology, University of Washington, Seattle, WA 98195, USA
C.J Cambier - Department of Immunology, University of Washington, Seattle, WA 98195, USA
J. Muse Davis - Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA 30322, USA
Christopher J Hall - Department of Molecular Medicines and Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Philip S Crosier - Department of Molecular Medicines and Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Lalita Ramakrishnan - Department of Microbiology, University of Washington, Seattle, WA 98195, USA
Resource Type: Journal article
Publication Details: Cell host & microbe, Vol.12(3), pp.301-312
DOI: 10.1016/j.chom.2012.07.009
PMID: 22980327
PMCID: PMC3638950
ISSN: 1931-3128
eISSN: 1934-6069
Grant note: R37 AI054503 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
Language: English
Date published: 09/13/2012
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093220602771

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