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Innate crosstalk of gamma delta T cells, neutrophils and monocytes in response to HMB-PP producing bacteria [Abstract]

Davey, Martin S., Heuston, S., Brown, A.. C., Walsh, Timothy Rutland, Toleman, Mark Alexander Howard, Gahan, C. G. M., Hill, C., Parish, T., Moser, Bernhard and Eberl, Matthias 2010. Innate crosstalk of gamma delta T cells, neutrophils and monocytes in response to HMB-PP producing bacteria [Abstract]. Immunology 131 , p. 63. 10.1111/j.1365-2567.2010.03390.x

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Recognition of invading bacterial pathogens by human peripheral blood cd T-cells is attributed to their unique TCR-mediated detection of the microbial metabolite, HMB-PP, although the exact mechanism behind cd T-cell access to this activating ligand is largely unclear. The response of cd T-cells to HMB-PP is likely to occur at early stages of infection and collectively with cells of the innate immune system. Here we assessed the crosstalk of autologous Vc9/Vd2 T-cells, neutrophils and monocytes in response to HMB-PP producing (e.g. Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Mycobacterium smegmatis) and HMB-PP deficient live bacteria (e.g. Staphylococcus aureus, Enterococcus faecalis, Chryseobacterium indologenes, Listeria innocua). Neutrophils harbouring HMB-PP producing but not HMB-PP deficient bacteria induced CD69 on Vc9/Vd2 T-cells and secretion of IFN-c and TNF-a. In addition, activation of Vc9/Vd2 Tcells only occurred with Listeria innocua transfected with HMB-PP synthase but not with HMB-PP deficient L. innocua wild-type, demonstrating that the response of Vc9/Vd2 T-cells to neutrophils harbouring phagocytosed bacteria depended on the ability of these bacteria to produce HMB-PP. Transwell experiments showed that Vc9/ Vd2 T-cells responded directly to soluble HMB-PP released from infected neutrophils and that cell-cell contact with monocytes was required for optimum activation. HMB-PP responsive Vc9/Vd2 T-cells also rescued neutrophils from spontaneous apoptosis and stimulated them to upregulate CD11b, shed CD62L, and release IL-8. Our findings link the essential innate function of pathogen clearance by neutrophils to the activation of cd T-cells, implicating an unconventional mechanism of pathogen recognition with the ability to potentiate innate and adaptive immunity. BSI 2010 Abstracts Selected for Poster Presentations

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Publisher: Wiley
ISSN: 1365-2567
Last Modified: 06 Sep 2020 15:22

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