Human MAIT Cells Respond to Staphylococcus aureus with Enhanced Anti-Bacterial Activity

Cooper, Andrew J.; Clegg, Jonah; Cassidy, Féaron C.; Hogan, Andrew E.; McLoughlin, Rachel M.

doi:10.3390/microorganisms10010148

Cited by 10 publications

(7 citation statements)

References 91 publications

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“…MAIT cells can be activated in two distinct manners, TCR dependent activation via MR1 presentation of microbial antigens or TCR independent activation via cytokines such as IL-18 (7,11). Upon activation, MAIT cells can rapidly produce a wide range of cytokines and lytic molecules including interferon (IFN)g, interleukin(IL)-17 and granzyme B, which supports MAIT cell host defensive responses (12)(13)(14)(15). Several studies have demonstrated that MAIT cells can lyse both bacterially infected cells and transformed malignant cells in an MR1 dependent manner (14)(15)(16).…”

Section: Mait Cell Basicsmentioning

confidence: 99%

“…Upon activation, MAIT cells can rapidly produce a wide range of cytokines and lytic molecules including interferon (IFN)g, interleukin(IL)-17 and granzyme B, which supports MAIT cell host defensive responses (12)(13)(14)(15). Several studies have demonstrated that MAIT cells can lyse both bacterially infected cells and transformed malignant cells in an MR1 dependent manner (14)(15)(16). MAIT cells can also be activated independent of their TCR via innate cytokines, the best described being IL-12, IL-18 and type 1 interferons (11,(17)(18)(19)(20).…”

Section: Mait Cell Basicsmentioning

confidence: 99%

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MAITabolism2 – the emerging understanding of MAIT cell metabolism and their role in metabolic disease

Kedia-Mehta

Hogan²

2023

Front. Immunol.

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Mucosal associated invariant T (MAIT) cells are a population of unconventional innate T cells due to their non-MHC restriction and rapid effector responses. MAIT cells can recognise bacterial derived antigens presented on the MHC-like protein via their semi-restricted T cell receptor (TCR). Upon TCR triggering MAIT cells rapidly produce a range of effector molecules including cytokines, lytic granules and chemokines. This rapid and robust effector response makes MAIT cells critical in host responses against many bacterial pathogens. MAIT cells can also respond independent of their TCR via innate cytokines such as interleukin (IL)-18, triggering cytokine production, and are important in anti-viral responses. In addition to their protective role, MAIT cells have been implicated in numerous inflammatory diseases, including metabolic diseases often contributing to the pathogenesis via their robust cytokine production. Effector cells such as MAIT cells require significant amounts of energy to support their potent responses, and the type of nutrients available can dictate the functionality of the cell. Although data on MAIT cell metabolism is just emerging, several recent studies are starting to define the intrinsic metabolic requirements and regulators of MAIT cells. In this review we will outline our current understanding of MAIT cell metabolism, and outline their role in metabolic disease, and how disease-related changes in extrinsic metabolism can alter MAIT cell responses.

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Section: Mait Cell Basicsmentioning

confidence: 99%

Section: Mait Cell Basicsmentioning

confidence: 99%

MAITabolism2 – the emerging understanding of MAIT cell metabolism and their role in metabolic disease

Kedia-Mehta

Hogan²

2023

Front. Immunol.

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“…Co-culture of MAIT and dendritic cells infected with S. aureus enhances IFN-γ and granzyme B production and degranulation. Granzyme B has direct anti-staphylococcal activity and promotes neutrophil-mediated clearance of SA infected cells, reducing intracellular persistence of S. aureus ( Cooper et al., 2022 ). Hence, vitamins and MAIT may play a key role in resolving S. aureus infections.…”

Section: Immune Responses and Vitaminsmentioning

confidence: 99%

Staphylococcus aureus adaptive evolution: Recent insights on how immune evasion, immunometabolic subversion and host genetics impact vaccine development

Lung

Chan

Prince

et al. 2022

Front. Cell. Infect. Microbiol.

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Despite meritorious attempts, a S. aureus vaccine that prevents infection or mitigates severity has not yet achieved efficacy endpoints in prospective, randomized clinical trials. This experience underscores the complexity of host-S. aureus interactions, which appear to be greater than many other bacterial pathogens against which successful vaccines have been developed. It is increasingly evident that S. aureus employs strategic countermeasures to evade or exploit human immune responses. From entering host cells to persist in stealthy intracellular reservoirs, to sensing the environmental milieu and leveraging bacterial or host metabolic products to reprogram host immune responses, S. aureus poses considerable challenges for the development of effective vaccines. The fact that this pathogen causes distinct types of infections and can undergo transient genetic, transcriptional or metabolic adaptations in vivo that do not occur in vitro compounds challenges in vaccine development. Notably, the metabolic versatility of both bacterial and host immune cells as they compete for available substrates within specific tissues inevitably impacts the variable repertoire of gene products that may or may not be vaccine antigens. In this respect, S. aureus has chameleon phenotypes that have alluded vaccine strategies thus far. Nonetheless, a number of recent studies have also revealed important new insights into pathogenesis vulnerabilities of S. aureus. A more detailed understanding of host protective immune defenses versus S. aureus adaptive immune evasion mechanisms may offer breakthroughs in the development of effective vaccines, but at present this goal remains a very high bar. Coupled with the recent advances in human genetics and epigenetics, newer vaccine technologies may enable such a goal. If so, future vaccines that protect against or mitigate the severity of S. aureus infections are likely to emerge at the intersection of precision and personalized medicine. For now, the development of S. aureus vaccines or alternative therapies that reduce mortality and morbidity must continue to be pursued.

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“…Mucosal Associated Invariant T (MAIT) cells are a population of unconventional T cells which are important in the immune defence against bacterial and viral infections 1, 2, 3, 4, 5, 6 . MAIT cells are restricted by the MHC-like molecule MR1 5 , and recognise a limited set of bacterially derived antigens 7 .…”

Section: Introductionmentioning

confidence: 99%

Glycogen-fuelled metabolism supports rapid Mucosal Associated Invariant T cell responses

Cassidy

Kedia-Mehta

Bergin

et al. 2022

Preprint

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Mucosal Associated Invariant T (MAIT) cells are a subset of unconventional T cells, which recognise a limited repertoire of ligands presented by the MHC class I-like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties and rapid effector functions, MAIT cells are emerging as attractive candidates for cancer-immunotherapy. In the current study, we demonstrate that MAIT cells are potent anti-tumour cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 hours. However, the metabolic processes supporting rapid MAIT cell anti-tumour responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 hours) cytokine production, as is oxidative phosphorylation. We show for the first time that MAIT cells have the machinery required to make and metabolize glycogen, and demonstrate that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show for the first time that glycogen-fuelled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications in their use as an immunotherapeutic agent.

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Human MAIT Cells Respond to Staphylococcus aureus with Enhanced Anti-Bacterial Activity

Cited by 10 publications

References 91 publications

MAITabolism2 – the emerging understanding of MAIT cell metabolism and their role in metabolic disease

MAITabolism2 – the emerging understanding of MAIT cell metabolism and their role in metabolic disease

Staphylococcus aureus adaptive evolution: Recent insights on how immune evasion, immunometabolic subversion and host genetics impact vaccine development

Glycogen-fuelled metabolism supports rapid Mucosal Associated Invariant T cell responses

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