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Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection

Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharma...

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Autores principales: Brigl, Manfred, Tatituri, Raju V.V., Watts, Gerald F.M., Bhowruth, Veemal, Leadbetter, Elizabeth A., Barton, Nathaniel, Cohen, Nadia R., Hsu, Fong-Fu, Besra, Gurdyal S., Brenner, Michael B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173255/
https://www.ncbi.nlm.nih.gov/pubmed/21555485
http://dx.doi.org/10.1084/jem.20102555
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author Brigl, Manfred
Tatituri, Raju V.V.
Watts, Gerald F.M.
Bhowruth, Veemal
Leadbetter, Elizabeth A.
Barton, Nathaniel
Cohen, Nadia R.
Hsu, Fong-Fu
Besra, Gurdyal S.
Brenner, Michael B.
author_facet Brigl, Manfred
Tatituri, Raju V.V.
Watts, Gerald F.M.
Bhowruth, Veemal
Leadbetter, Elizabeth A.
Barton, Nathaniel
Cohen, Nadia R.
Hsu, Fong-Fu
Besra, Gurdyal S.
Brenner, Michael B.
author_sort Brigl, Manfred
collection PubMed
description Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological α-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign lipid antigens is the main driver for iNKT cell activation during infection. However, when we compared the role of microbial antigens versus innate cytokine-driven mechanisms, we found that iNKT cell interferon-γ production after in vitro stimulation or infection with diverse bacteria overwhelmingly depended on toll-like receptor–driven IL-12. Importantly, activation of iNKT cells in vivo during infection with Sphingomonas yanoikuyae or Streptococcus pneumoniae, pathogens which are known to express iNKT cell antigens and which require iNKT cells for effective protection, also predominantly depended on IL-12. Constitutive expression of high levels of IL-12 receptor by iNKT cells enabled instant IL-12–induced STAT4 activation, demonstrating that among T cells, iNKT cells are uniquely equipped for immediate, cytokine-driven activation. These findings reveal that innate and cytokine-driven signals, rather than cognate microbial antigen, dominate in iNKT cell activation during microbial infections.
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spelling pubmed-31732552011-12-06 Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection Brigl, Manfred Tatituri, Raju V.V. Watts, Gerald F.M. Bhowruth, Veemal Leadbetter, Elizabeth A. Barton, Nathaniel Cohen, Nadia R. Hsu, Fong-Fu Besra, Gurdyal S. Brenner, Michael B. J Exp Med Article Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological α-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign lipid antigens is the main driver for iNKT cell activation during infection. However, when we compared the role of microbial antigens versus innate cytokine-driven mechanisms, we found that iNKT cell interferon-γ production after in vitro stimulation or infection with diverse bacteria overwhelmingly depended on toll-like receptor–driven IL-12. Importantly, activation of iNKT cells in vivo during infection with Sphingomonas yanoikuyae or Streptococcus pneumoniae, pathogens which are known to express iNKT cell antigens and which require iNKT cells for effective protection, also predominantly depended on IL-12. Constitutive expression of high levels of IL-12 receptor by iNKT cells enabled instant IL-12–induced STAT4 activation, demonstrating that among T cells, iNKT cells are uniquely equipped for immediate, cytokine-driven activation. These findings reveal that innate and cytokine-driven signals, rather than cognate microbial antigen, dominate in iNKT cell activation during microbial infections. The Rockefeller University Press 2011-06-06 /pmc/articles/PMC3173255/ /pubmed/21555485 http://dx.doi.org/10.1084/jem.20102555 Text en © 2011 Brigl et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Brigl, Manfred
Tatituri, Raju V.V.
Watts, Gerald F.M.
Bhowruth, Veemal
Leadbetter, Elizabeth A.
Barton, Nathaniel
Cohen, Nadia R.
Hsu, Fong-Fu
Besra, Gurdyal S.
Brenner, Michael B.
Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
title Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
title_full Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
title_fullStr Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
title_full_unstemmed Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
title_short Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
title_sort innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer t cell activation during microbial infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173255/
https://www.ncbi.nlm.nih.gov/pubmed/21555485
http://dx.doi.org/10.1084/jem.20102555
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