Cited by 394Tuberculosis Research and EpidemiologyAntimicrobial Peptides and ActivitiesImmune responses and vaccinations

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Neutrophil-mediated innate immune resistance to mycobacteria

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Martineau, Adrian R., Newton, Sandra M., Wilkinson, Katalin A., Kampmann, Beate, Hall, Bridget M., Nawroly, Niga, Packe, Geoffrey E., Davidson, Robert N., Griffiths, Christopher J., Wilkinson, Robert J.·2007·Journal of Clinical Investigation

DOI 10.1172/jci31097PMC PMC1904316

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Abstract

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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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)
ORCID: Martineau, Adrian R.
Newton, Sandra M.
Wilkinson, Katalin A.
Kampmann, Beate
Wilkinson, Robert J.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2007-07-02
Volume: 117
Issue: 7
Pages: 1988-1994
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci31097
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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Neutrophil-mediated innate immune resistance to mycobacteria

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