Abstract

Mucosal‐associated invariant T (MAIT) cells are an abundant human T‐cell subset with antimicrobial 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 T‐cell receptor‐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 Escherichia coli. THP‐1 cells were generally more potent in inducing IFNγ and IFNγ/TNF production by MAIT cells. Furthermore, THP‐1, 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.

Highlights

  • Mucosal-associated invariant T (MAIT) cells represent the most abundant innate-like T lymphocyte population within the human body comprising up to ~5% of total T cells.[1]

  • When CD8 T cells were co-cultured with THP-1 cells together with 20 bacteria per cell (BpC) E. coli, we observed IFNc expression in about 50% of the MAIT cells, which remained stable with increasing BpC (Figure 1c)

  • B cells (BCL) co-cultured with CD8 T cells and 20 BpC E. coli resulted in less than 20% IFNc+ MAIT cells (Figure 1b, c)

Read more

Summary

Introduction

Mucosal-associated invariant T (MAIT) cells represent the most abundant innate-like T lymphocyte population within the human body comprising up to ~5% of total T cells.[1]. Human MAIT cells are characterized by an effector memory phenotype (CCR7negCD62LloCD45ROposCD45RAneg CD95hi) suggesting an early detection of pathogens and a quick response to bacterial stimulation.[7,11] Early stages of bacterial recognition by MAIT cells are dominated by the MR1-dependent augmentation of TCR signaling, which leads to activation and IFNc production by MAIT cells.[6,8] MAIT cells react to MR1-expressing APCs, for example, dendritic cells, B cells and monocytes infected or cocultured with bacteria as well as bacterially infected epithelial cells.[4,6,8] The importance of MR1 in MAIT cell activation and in early control of certain pathogens is emphasized by the increased susceptibility to K. pneumoniae and Francisella tularensis infections in MR1-deficient mice.[9,12]

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.