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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.

Authors

Adrian R. Martineau ... Christopher J. Griffiths, Robert J. Wilkinson

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Citations to this article in year 2008 (9)

Title and authors Publication Year
Homeostatic regulation of blood neutrophil counts
S Vietinghoff, K Ley
Journal of immunology (Baltimore, Md. : 1950) 2008
Expression and secretion of cathelicidin LL-37 in human epithelial cells after infection by Mycobacterium bovis Bacillus Calmette-Guérin
P Méndez-Samperio, E Miranda, A Trejo
Clinical and vaccine immunology : CVI 2008
Determinants of natural immunity against tuberculosis in an endemic setting: factors operating at the level of macrophage-Mycobacterium tuberculosis interaction
AN Gaikwad, S Sinha
Clinical & Experimental Immunology 2008
Mycobacterium bovis BCG-infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice
C Morel, E Badell, V Abadie, M Robledo, N Setterblad, JC Gluckman, B Gicquel, S Boudaly, N Winter
European Journal of Immunology 2008
Mice That Overexpress CC Chemokine Ligand 2 in Their Lungs Show Increased Protective Immunity to Infection withMycobacterium bovisBacille Calmette‐Guérin
O Schreiber, K Steinwede, N Ding, M Srivastava, R Maus, F Länger, J Prokein, S Ehlers, T Welte, MD Gunn, UA Maus
The Journal of Infectious Diseases 2008
Vitamin D in the treatment and prevention of tuberculosis
AR Martineau, CJ Griffiths, RJ Wilkinson
Expert Review of Endocrinology & Metabolism 2008
Innate immunity in tuberculosis: myths and truth
DS Korbel, BE Schneider, UE Schaible
Microbes and Infection 2008
Neutrophils recruited to the site of Mycobacterium bovis BCG infection undergo apoptosis and modulate lipid body biogenesis and prostaglandin E production by macrophages
H D'Avila, NR Roque, RM Cardoso, HC Castro-Faria-Neto, RC Melo, PT Bozza
Cellular Microbiology 2008
Update in Tuberculosis 2007
WW Yew, CC Leung
American journal of respiratory and critical care medicine 2008

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