期刊
JOURNAL OF IMMUNOLOGY
卷 193, 期 7, 页码 3704-3716出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1401018
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资金
- United Kingdom Clinical Research Network Study Portfolio
- National Institute for Social Care and Health Research (NISCHR)
- NISCHR/Wellcome Trust Institutional Strategic Support Fund
- Sevemside Alliance for Translational Research/South East Wales Academic Health Science Partnership Health Technology Challenge Scheme
- European Union-Framework Programme 7 Marie Curie Initial Training Network European Training and Research in Peritoneal Dialysis,a Medical Research Council Ph.D. studentship
- Cancer Research UK
- Cancer Research UK [13823] Funding Source: researchfish
- Medical Research Council [1280996] Funding Source: researchfish
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. V gamma 9/V delta 2 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-gamma, and TNF-alpha. 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 V gamma 9/V delta 2 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.
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