Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α

• Published in: Nature (London) 1996-05, Vol.381 (6577), p.77-80
• Main Authors: Malaviya, Ravi, Ikeda, Teruo, Ross, Elaine, Abraham, Soman N
• Format: Article
• Language: English
• Subjects: Adhesins, Bacterial - immunology; Adhesins, Escherichia coli; Analysis of the immune response. Humoral and cellular immunity; Animals; Bacteria; Bacterial diseases; Biological and medical sciences; Cellular biology; Chemotaxis, Leukocyte; Escherichia coli - immunology; Fimbriae Proteins; Fimbriae, Bacterial - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humanities and Social Sciences; Hypersensitivity; Immunobiology; Infections; Klebsiella Infections - immunology; Klebsiella Infections - microbiology; Klebsiella pneumoniae; letter; Lung - immunology; Lung - microbiology; Mast Cells - immunology; Mice; multidisciplinary; Neutrophils - immunology; Organs and cells involved in the immune response; Peritonitis - immunology; Peritonitis - microbiology; Pneumonia, Bacterial - immunology; Pneumonia, Bacterial - microbiology; Recombinant Proteins - immunology; Rodents; Science; Science (multidisciplinary); Tumor Necrosis Factor-alpha - immunology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/381077a0

ALTHOUGH mast cells have been implicated in a variety of inflammatory conditions including immediate hypersensitivity and interstitial cystitis, 1,2 their physiological role in the body is unknown. We investigated the role of mast cells in host defence against bacterial infections using a well characterized mast-cell-deficiency mouse model 3,4 . We report here that mast cells, which are selectively located at portals of bacterial entry, are important to host defence. Mast-cell-deficient WBB6F1-W/W v mice (W/W v ) were up to 20-fold less efficient in clearing enterobacteria than control WBB6F1+/+ (+/+) mice or mast-cell-reconstituted W/W v (W/W v + MC) mice. With higher bacterial inocula, only W/W v mice died (80%). The limited bacterial clearance in W/W v mice directly correlated with impaired neutrophil influx. The mast-cell chemoattractant TNF-α was implicated in the neutrophil response because TNF-α was locally released only in +/+ and W/W v + MC mice, TNF-α-specific antibodies blocked over 70% of the neutrophil influx, and purified mast cells released TNF-α upon incubation with bacteria. Additionally, the type-1 fimbrial subunit, FimH, was the necessary enterobacterial component for mast-cell activation and neutrophil influx because an isogenic FimH – mutant evoked a limited neutrophil response in +/+ mice compared to wild-type bacteria.