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 ORCID: https://orcid.org/0000-0003-4315-4096, Toleman, Mark Alexander Howard ORCID: https://orcid.org/0000-0002-9497-0512, Gahan, C. G. M., Hill, C., Parish, T., Moser, Bernhard ORCID: https://orcid.org/0000-0002-4354-4572 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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Abstract

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:	19 Oct 2022 10:02
URI:	https://orca.cardiff.ac.uk/id/eprint/23004

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