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Co-ordinated crosstalk of human gamma delta T cells, neutrophils and monocytes in response to bacterial infections [Abstract]

Davey, Martin S., Moser, Bernhard and Eberl, Matthias 2011. Co-ordinated crosstalk of human gamma delta T cells, neutrophils and monocytes in response to bacterial infections [Abstract]. Immunology 135 (s1) , p. 85.

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Abstract

Human Vc9/Vd2-T-cells constitute 15% of all peripheral blood Tcells under normal conditions but can rapidly increase to over 50% in acute infection. The direct recognition of invading pathogens by Vc9/ Vd2-T-cells is attributed to their unique TCR-mediated detection of the microbial metabolite, HMB-PP. We have identified a crucial role played by infiltrating neutrophils in their ability to facilitate the release of functional HMB-PP from phagocytosed bacteria. Neutrophils harbouring HMB-PP over-expressing but not HMB-PP deficient bacteria induced potent cd-T-cell cytokine responses (IFN-c and TNF). Transwell experiments showed that cd-T-cells responded directly to soluble HMB-PP released from infected neutrophils and that cell-cell contact with monocytes was required for optimum activation. We observed this crosstalk with autologous cd-T-cells, neutrophils and monocytes in response to HMB-PP producing (e.g. Klebsiella, Enterobacter, Pseudomonas) and HMB-PP deficient live bacterial pathogens (e.g. Staphylococcus, Enterococcus, Chryseobacterium). Monocytes provide a key presenting mechanism for microbe derived HMB-PP whereby they take up and directly present this activator to induce cd-T-cell responses; this could be blocked by the use of various inhibitors of monocyte endocytosis. Microbe responsive cd-T-cells also interacted with neutrophils by providing potent long-lived survival and activation signals. We have also observed similar activation marker expression on neutrophils and cd-T-cells in patients with sepsis. Taken together our findings define an unconventional mechanism of pathogen recognition, which links the crucial innate function of pathogen clearance by neutrophils with an alternative antigen processing pathway in monocytes, resulting in the highly co-ordinated activation of cd-T-cells and potentiation of the cellular immune response.

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 Sep 2019 14:25
URI: http://orca-mwe.cf.ac.uk/id/eprint/23009

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