Microbe-specific unconventional t cells induce human neutrophil differentiation into antigen cross-presenting cells

Martin S. Davey, Matt P. Morgan, Anna Rita Liuzzi, Christopher J. Tyler, Mohd Wajid A. Khan, Tamas Szakmany, Judith E. Hall, Bernhard Moser, Matthias Eberl

Research output: Contribution to journalArticleResearchpeer-review

58 Citations (Scopus)

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. Vg9/ Vd2 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.

Original languageEnglish
Pages (from-to)3704-3716
Number of pages13
JournalJournal of Immunology
Volume193
Issue number7
DOIs
Publication statusPublished - 1 Oct 2014
Externally publishedYes

Cite this