Activation of human γδ T cells and NK cells by Staphylococcal enterotoxins requires both monocytes and conventional T cells
(2022) In Journal of Leukocyte Biology 111(3). p.597-609- Abstract
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... (More)
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.
(Less)
- author
- Mata Forsberg, Manuel ; Arasa, Claudia ; van Zwol, Willemien ; Uzunçayir, Sibel LU ; Schönbichler, Anna ; Regenthal, Paulina LU ; Schelin, Jenny LU ; Lindkvist-Petersson, Karin LU ; Björkander, Sophia and Sverremark-Ekström, Eva
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- MAIT cell, SEA, SEH, TSST-1, unconventional T cells
- in
- Journal of Leukocyte Biology
- volume
- 111
- issue
- 3
- pages
- 597 - 609
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85107638406
- pmid:34114693
- ISSN
- 0741-5400
- DOI
- 10.1002/JLB.3A1020-630RR
- language
- English
- LU publication?
- yes
- id
- d6dbd00c-a731-4819-bc8d-ea13d98eb12b
- date added to LUP
- 2021-07-06 11:31:37
- date last changed
- 2024-06-15 13:18:01
@article{d6dbd00c-a731-4819-bc8d-ea13d98eb12b,
abstract = {{<p>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.</p>}},
author = {{Mata Forsberg, Manuel and Arasa, Claudia and van Zwol, Willemien and Uzunçayir, Sibel and Schönbichler, Anna and Regenthal, Paulina and Schelin, Jenny and Lindkvist-Petersson, Karin and Björkander, Sophia and Sverremark-Ekström, Eva}},
issn = {{0741-5400}},
keywords = {{MAIT cell; SEA; SEH; TSST-1; unconventional T cells}},
language = {{eng}},
number = {{3}},
pages = {{597--609}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Leukocyte Biology}},
title = {{Activation of human γδ T cells and NK cells by Staphylococcal enterotoxins requires both monocytes and conventional T cells}},
url = {{http://dx.doi.org/10.1002/JLB.3A1020-630RR}},
doi = {{10.1002/JLB.3A1020-630RR}},
volume = {{111}},
year = {{2022}},
}