Neutrophil-mediated innate immune resistance to mycobacteria
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Neutrophils contain antimicrobial peptides with antituberculous activity, but their contribution to immune resistance to tuberculosis (TB) infection has not been previously investigated to our knowledge. We determined differential white cell counts in peripheral blood of 189 adults who had come into contact with patients diagnosed with active TB in London, United Kingdom, and evaluated them for evidence of TB infection and capacity to restrict mycobacterial growth in whole-blood assays. Risk of TB infection was inversely and independently associated with peripheral blood neutrophil count in contacts of patients diagnosed with pulmonary TB. The ability of whole blood to restrict growth of Mycobacterium bovis bacille Calmette Guérin and Mycobacterium tuberculosis was impaired 7.3- and 3.1-fold, respectively, by neutrophil depletion. In microbiological media, human neutrophil peptides (HNPs) 1-3 killed M. tuberculosis. The neutrophil peptides cathelicidin LL-37 and lipocalin 2 restricted growth of the organism, the latter in an iron-dependent manner. Black African participants had lower neutrophil counts and lower circulating concentrations of HNP1-3 and lipocalin 2 than south Asian and white participants. Neutrophils contribute substantially to innate resistance to TB infection, an activity associated with their antimicrobial peptides. Elucidation of the regulation of neutrophil antimicrobial peptides could facilitate prevention and treatment of TB.
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Increased susceptibility of Lcn2−/− mice to mycobacterial infections might be due to Lcn2's function as a chemoattractant for neutrophils rather than iron sequestration.
“Importantly, Lcn2−/− mice are more susceptible to mycobacterial infections (214), which might be different from the iron-sequestrating role of Lcn2 (215) but rather due to its function as efficient chemoattractant for neutrophils to sites of infection (216–218).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [215]
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- Authors
- Martineau, A. R., Newton, S. M., Wilkinson, K. A., Kampmann, B., Hall, B. M., Nawroly, N., Packe, G. E., Davidson, R. N., Griffiths, C. J., & Wilkinson, R. J.
- Affiliations
- Imperial College London (GB)
- University of Cape Town (ZA)
- Queen Mary University of London (GB)
- Newham University Hospital (GB)
- Northwick Park Hospital (GB)
- Venue
- Journal of Clinical Investigation
- Published
- 2007-07-02
- Volume
- 117
- Issue
- 7
- Pages
- 1988-1994
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1904316
- OpenAlex
- W2014262351
- Cited by
- 394
- References
- 37
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 13 · 2023: 16 · 2022: 15 · 2021: 23 · 2020: 15 · 2019: 31 · 2018: 27 · 2017: 29 · 2016: 19 · 2015: 21 · 2014: 26 · 2013: 29 · 2012: 20
- FWCI
- 11.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (077273, 072070, 066321, 064261)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- neutrophils, tuberculosis, Mycobacterium tuberculosis, Mycobacterium bovis BCG, antimicrobial peptides, human neutrophil peptides, cathelicidin LL-37, neutrophil gelatinase-associated lipocalin, innate immunity, TB contacts, neutrophil depletion, ethnic differences
- MeSH terms
- Female, Humans, Immunity, Innate, Leukocyte Count, Male, Mycobacterium bovis, Mycobacterium tuberculosis, Neutrophils, Tuberculosis, Cytokines
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