title: Microbe-specific unconventional T cells induce human neutrophil differentiation into antigen cross-presenting cells.
abstract: The early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. However, there is emerging evidence that neutrophils play additional effector and regulatory roles. The present study demonstrates that human neutrophils assume Ag cross-presenting functions and suggests a plausible scenario for the local generation of APC-like neutrophils through the mobilization of unconventional T cells in response to microbial metabolites. Vγ9/Vδ2 T cells and mucosal-associated invariant T cells are abundant in blood, inflamed tissues, and mucosal barriers. In this study, both human cell types responded rapidly to neutrophils after phagocytosis of Gram-positive and Gram-negative bacteria producing the corresponding ligands, and in turn mediated the differentiation of neutrophils into APCs for both CD4(+) and CD8(+) T cells through secretion of GM-CSF, IFN-γ, and TNF-α. In patients with acute sepsis, circulating neutrophils displayed a similar APC-like phenotype and readily processed soluble proteins for cross-presentation of antigenic peptides to CD8(+) T cells, at a time when peripheral Vγ9/Vδ2 T cells were highly activated. Our findings indicate that unconventional T cells represent key controllers of neutrophil-driven innate and adaptive responses to a broad range of pathogens.
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Davey
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.|Cardiff & Vale University Health Board, Cardiff CF14 4XW, United Kingdom.
authors.forename: Matt P
authors.initials: MP
authors.lastname: Morgan
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Liuzzi
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Tyler
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Mohd Wajid A
authors.initials: MWA
authors.lastname: Khan
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.|Cwm Taf University Health Board, Llantrisant CF72 8XR, United Kingdom.
authors.forename: Tamas
authors.initials: T
authors.lastname: Szakmany
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Hall
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.affiliation: Cardiff Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eberl
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D045142:Cross-Priming; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta