Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism

Mucosal-associated invariant T (MAIT) cells are an abundant human T cell subset with anti-microbial properties. They can respond to bacteria presented via antigen-presenting cells (APCs) such as macrophages, which present bacterially derived ligands from the riboflavin synthesis pathway on MR1. More...

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Main Authors: Banki, Z, Krabbendam, L, Klaver, D, Leng, T, Kruis, S, Mehta, H, Müllauer, B, Orth-Höller, D, Stoiber, H, Willberg, C, Klenerman, P
格式: Journal article
出版: Wiley 2019
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author Banki, Z
Krabbendam, L
Klaver, D
Leng, T
Kruis, S
Mehta, H
Müllauer, B
Orth-Höller, D
Stoiber, H
Willberg, C
Klenerman, P
author_facet Banki, Z
Krabbendam, L
Klaver, D
Leng, T
Kruis, S
Mehta, H
Müllauer, B
Orth-Höller, D
Stoiber, H
Willberg, C
Klenerman, P
author_sort Banki, Z
collection OXFORD
description Mucosal-associated invariant T (MAIT) cells are an abundant human T cell subset with anti-microbial properties. They can respond to bacteria presented via antigen-presenting cells (APCs) such as macrophages, which present bacterially derived ligands from the riboflavin synthesis pathway on MR1. Moreover, MAIT cells are also highly responsive to cytokines which enhance and even substitute for TCR-mediated signaling. The mechanisms leading to an efficient presentation of bacteria to MAIT cells by APCs have not been fully elucidated. Here we showed that the monocytic cell line THP-1 and B cells activated MAIT cells differentially in response to E. coli. THP-1 cells were generally more potent in inducing IFNγ and IFNγ/TNF production by MAIT cells. Furthermore, THP-1 cells but not B cells produced TNF upon bacterial stimulation, which in turn supported IFNγ production by MAIT cells. Finally, we addressed the role of antibody-dependent opsonization of bacteria in the activation of MAIT cells using in vitro models. We found that opsonization had a substantial impact on downstream MAIT cell activation by monocytes. This was associated with enhanced activation of monocytes and increased TNF release. Importantly, this TNF acted in concert with other cytokines to drive MAIT cell activation. These data indicate both a significant interaction between adaptive and innate immunity in the response to bacteria, and an important role for TNF in MAIT cell triggering.
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spelling oxford-uuid:5a0b94f4-ab8b-4b40-9c5c-7b46f2c135412022-03-26T17:13:24ZAntibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanismJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5a0b94f4-ab8b-4b40-9c5c-7b46f2c13541Symplectic Elements at OxfordWiley2019Banki, ZKrabbendam, LKlaver, DLeng, TKruis, SMehta, HMüllauer, BOrth-Höller, DStoiber, HWillberg, CKlenerman, PMucosal-associated invariant T (MAIT) cells are an abundant human T cell subset with anti-microbial properties. They can respond to bacteria presented via antigen-presenting cells (APCs) such as macrophages, which present bacterially derived ligands from the riboflavin synthesis pathway on MR1. Moreover, MAIT cells are also highly responsive to cytokines which enhance and even substitute for TCR-mediated signaling. The mechanisms leading to an efficient presentation of bacteria to MAIT cells by APCs have not been fully elucidated. Here we showed that the monocytic cell line THP-1 and B cells activated MAIT cells differentially in response to E. coli. THP-1 cells were generally more potent in inducing IFNγ and IFNγ/TNF production by MAIT cells. Furthermore, THP-1 cells but not B cells produced TNF upon bacterial stimulation, which in turn supported IFNγ production by MAIT cells. Finally, we addressed the role of antibody-dependent opsonization of bacteria in the activation of MAIT cells using in vitro models. We found that opsonization had a substantial impact on downstream MAIT cell activation by monocytes. This was associated with enhanced activation of monocytes and increased TNF release. Importantly, this TNF acted in concert with other cytokines to drive MAIT cell activation. These data indicate both a significant interaction between adaptive and innate immunity in the response to bacteria, and an important role for TNF in MAIT cell triggering.
spellingShingle Banki, Z
Krabbendam, L
Klaver, D
Leng, T
Kruis, S
Mehta, H
Müllauer, B
Orth-Höller, D
Stoiber, H
Willberg, C
Klenerman, P
Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism
title Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism
title_full Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism
title_fullStr Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism
title_full_unstemmed Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism
title_short Antibody opsonization enhances MAIT cell responsiveness to bacteria via a TNF-dependent mechanism
title_sort antibody opsonization enhances mait cell responsiveness to bacteria via a tnf dependent mechanism
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