Neutrophils Exert Protection in the Early Tuberculous Granuloma by Oxidative Killing of Mycobacteria Phagocytosed from Infected Macrophages
Open accessAbstract
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.
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The aim of recruited neutrophils is to take up mycobacteria released from dying macrophages and rapidly kill them.
“The aim of these neutrophils is to take up such mycobacteria and to rapidly kill them (112).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [112]
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- Authors
- Yang, C.-T., Cambier, C. J., Davis, J. M., Hall, C. J., Crosier, P. S., & Ramakrishnan, L.
- Affiliations
- University of Washington (US)
- Emory University (US)
- University of Auckland (NZ)
- Corresponding author
- Ramakrishnan, Lalita
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 12
- Issue
- 3
- Pages
- 301-312
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3638950
- OpenAlex
- W2102467166
- Cited by
- 293
- References
- 66
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 11 · 2023: 19 · 2022: 16 · 2021: 17 · 2020: 24 · 2019: 28 · 2018: 13 · 2017: 27 · 2016: 25 · 2015: 25 · 2014: 28 · 2013: 29 · 2012: 3
- FWCI
- 18.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Funders
- U.S. Public Health Service (R01 A154503, R01 A136396)
- National Institute of Mental Health (DP1MH099901)
- National Institute of Allergy and Infectious Diseases (R01AI036396, R37AI054503)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- neutrophils, tuberculosis, tuberculous granuloma, Mycobacterium marinum, Mycobacterium tuberculosis, NADPH oxidase, oxidative killing, phagocytosis, infected macrophages, granuloma formation, neutrophil recruitment, chronic granulomatous disease, zebrafish infection model
- MeSH terms
- Animals, Granuloma, Humans, Macrophages, Molecular Sequence Data, NADP, Neutrophils, Oxidation-Reduction, Oxidoreductases, Zebrafish, Sequence Analysis, DNA, Oxidative Stress, Mycobacterium marinum, Microbial Viability
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