Activation of human γδ T cells and NK cells by Staphylococcal enterotoxins requires both monocytes and conventional T cells

Manuel Mata Forsberg, Claudia Arasa, Willemien van Zwol, Sibel Uzunçayir, Anna Schönbichler, Paulina Regenthal, Jenny Schelin, Karin Lindkvist-Petersson, Sophia Björkander, Eva Sverremark-Ekström

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Staphylococcal enterotoxins (SE) pose a great threat to human health due to their ability to bypass antigen presentation and activate large amounts of conventional T cells resulting in a cytokine storm potentially leading to toxic shock syndrome. Unconventional T- and NK cells are also activated by SE but the mechanisms remain poorly understood. In this study, the authors aimed to explore the underlying mechanism behind SE-mediated activation of MAIT-, γδ T-, and NK cells in vitro. CBMC or PBMC were stimulated with the toxins SEA, SEH, and TSST-1, and cytokine and cytotoxic responses were analyzed with ELISA and flow cytometry. All toxins induced a broad range of cytokines, perforin and granzyme B, although SEH was not as potent as SEA and TSST-1. SE-induced IFN-γ expression in MAIT-, γδ T-, and NK cells was clearly reduced by neutralization of IL-12, while cytotoxic compounds were not affected at all. Kinetic assays showed that unconventional T cell and NK cell-responses are secondary to the response in conventional T cells. Furthermore, co-cultures of isolated cell populations revealed that the ability of SEA to activate γδ T- and NK cells was fully dependent on the presence of both monocytes and αβ T cells. Lastly, it was found that SE provoked a reduced and delayed cytokine response in infants, particularly within the unconventional T and NK cell populations. This study provides novel insights regarding the activation of unconventional T- and NK cells by SE, which contribute to understanding the vulnerability of young children towards Staphylococcus aureus infections.

Originalspråkengelska
TidskriftJournal of Leukocyte Biology
DOI
StatusE-pub ahead of print - 2021

Ämnesklassifikation (UKÄ)

  • Immunologi inom det medicinska området
  • Cell- och molekylärbiologi
  • Mikrobiologi inom det medicinska området

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