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

2022 ◽  
Vol 10 (1) ◽  
pp. 148
Author(s):  
Andrew J. R. Cooper ◽  
Jonah Clegg ◽  
Féaron C. Cassidy ◽  
Andrew E. Hogan ◽  
Rachel M. McLoughlin
Keyword(s):  
Staphylococcus Aureus ◽  
Cytokine Production ◽  
Cell Cytotoxicity ◽  
Mait Cells ◽  
Cell Responses ◽  
Potential Applications ◽  
Infected Cells ◽  
Great Relevance ◽  
Ongoing Development ◽  
Mait Cell

Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT cells is to defend against Staphylococcus aureus, a pathogen of serious clinical significance. However, it is unknown how MAIT cell responses to S. aureus are elicited, nor has it been investigated whether MAIT cell cytotoxicity is mobilized against intracellular S. aureus. In this study, we investigate the capacity of human MAIT cells to respond directly to S. aureus. MAIT cells co-cultured with dendritic cells (DCs) infected with S. aureus rapidly upregulate CD69, express IFNγ and Granzyme B and degranulate. DC secretion of IL-12, but not IL-18, was implicated in this immune response, while TCR binding of MR1 is required to commence cytokine production. MAIT cell cytotoxicity resulted in apoptosis of S. aureus-infected cells, and reduced intracellular persistence of S. aureus. These findings implicate these unconventional T cells in important, rapid anti-S. aureus responses that may be of great relevance to the ongoing development of novel anti-S. aureus treatments.

scholarly journals Sustained IFN-I stimulation impairs MAIT cell responses to bacteria by inducing IL-10 during chronic HIV-1 infection

2020 ◽  
Vol 6 (8) ◽  
pp. eaaz0374 ◽  
Author(s):  
X. Tang ◽  
S. Zhang ◽  
Q. Peng ◽  
L. Ling ◽  
H. Shi ◽  
...  
Keyword(s):  
Cell Activation ◽  
Surface Protein ◽  
Interleukin 10 ◽  
Mait Cells ◽  
Cell Dysfunction ◽  
Cell Responses ◽  
High Level ◽  
Hiv 1 ◽  
Mait Cell

Mucosal-associated invariant T (MAIT) cells in HIV-1–infected individuals are functionally impaired by poorly understood mechanisms. Single-cell transcriptional and surface protein analyses revealed that peripheral MAIT cells from HIV-1–infected subjects were highly activated with the up-regulation of interferon (IFN)–stimulated genes as compared to healthy individuals. Sustained IFN-α treatment suppressed MAIT cell responses to Escherichia coli by triggering high-level interleukin-10 (IL-10) production by monocytes, which subsequently inhibited the secretion of IL-12, a crucial costimulatory cytokine for MAIT cell activation. Blocking IFN-α or IL-10 receptors prevented MAIT cell dysfunction induced by HIV-1 exposure in vitro. Moreover, blocking the IL-10 receptor significantly improved anti–Mycobacterium tuberculosis responses of MAIT cells from HIV-1–infected patients. Our findings demonstrate the central role of the IFN-I/IL-10 axis in MAIT cell dysfunction during HIV-1 infection, which has implications for the development of anti–IFN-I/IL-10 strategies against bacterial coinfections in HIV-1–infected patients.

scholarly journals Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines

2017 ◽  
Vol 114 (27) ◽  
pp. E5434-E5443 ◽  
Author(s):  
Joana Dias ◽  
Edwin Leeansyah ◽  
Johan K. Sandberg
Keyword(s):  
Killer Cell ◽  
Cell Subset ◽  
Effector Memory ◽  
Response Patterns ◽  
E Coli ◽  
Mait Cells ◽  
Cell Responses ◽  
Fungal Organisms ◽  
Subset Diversity ◽  
Mait Cell

Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway. The ability of MAIT cells to exhibit microbe-specific functional specialization has not been thoroughly investigated. Here, we found that MAIT cell responses against Escherichia coli and Candida albicans displayed microbe-specific polyfunctional response profiles, antigen sensitivity, and response magnitudes. MAIT cell effector responses against E. coli and C. albicans displayed differential MR1 dependency and TCR β-chain bias, consistent with possible divergent antigen subspecificities between these bacterial and fungal organisms. Finally, although the MAIT cell immunoproteome was overall relatively homogenous and consistent with an effector memory-like profile, it still revealed diversity in a set of natural killer cell-associated receptors. Among these, CD56, CD84, and CD94 defined a subset with higher expression of the transcription factors promyelocytic leukemia zinc finger (PLZF), eomesodermin, and T-bet and enhanced capacity to respond to IL-12 and IL-18 stimulation. Thus, the conserved and innate-like MAIT cells harbor multiple layers of functional heterogeneity as they respond to bacterial or fungal organisms or innate cytokines and adapt their antimicrobial response patterns in a stimulus-specific manner.

scholarly journals Human MAIT-cell responses toEscherichia coli: activation, cytokine production, proliferation, and cytotoxicity

2016 ◽  
Vol 100 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Joana Dias ◽  
Michał J. Sobkowiak ◽  
Johan K. Sandberg ◽  
Edwin Leeansyah
Keyword(s):  
Cytokine Production ◽  
Cell Responses ◽  
Mait Cell

scholarly journals Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19

2020 ◽  
Author(s):  
Chen Yu ◽  
Sejiro Littleton ◽  
Nicholas Giroux ◽  
Rose Mathew ◽  
Shengli Ding ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Gene Signature ◽  
Peripheral Blood Mononuclear ◽  
Color Flow ◽  
Sexual Dimorphisms ◽  
Mait Cells ◽  
Cell Responses ◽  
Female Specific ◽  
Pronounced Reduction ◽  
Mait Cell

ABSTRACTSexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.

scholarly journals MAIT Cells and Microbiota in Multiple Sclerosis and Other Autoimmune Diseases

2021 ◽  
Vol 9 (6) ◽  
pp. 1132
Author(s):  
Rosella Mechelli ◽  
Silvia Romano ◽  
Carmela Romano ◽  
Emanuele Morena ◽  
Maria Chiara Buscarinu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Tissue Repair ◽  
Disease Course ◽  
Common Features ◽  
Mait Cells ◽  
Cell Responses ◽  
Clinical Biomarkers ◽  
Autoimmune Conditions ◽  
Treatment Naïve ◽  
Mait Cell

The functions of mucosal-associated invariant T (MAIT) cells in homeostatic conditions include the interaction with the microbiota and its products, the protection of body barriers, and the mounting of a tissue-repair response to injuries or infections. Dysfunction of MAIT cells and dysbiosis occur in common chronic diseases of inflammatory, metabolic, and tumor nature. This review is aimed at analyzing the changes of MAIT cells, as well as of the microbiota, in multiple sclerosis and other autoimmune disorders. Common features of dysbiosis in these conditions are the reduced richness of microbial species and the unbalance between pro-inflammatory and immune regulatory components of the gut microbiota. The literature concerning MAIT cells in these disorders is rather complex, and sometimes not consistent. In multiple sclerosis and other autoimmune conditions, several studies have been done, or are in progress, to find correlations between intestinal permeability, dysbiosis, MAIT cell responses, and clinical biomarkers in treated and treatment-naïve patients. The final aims are to explain what activates MAIT cells in diseases not primarily infective, which interactions with the microbiota are potentially pathogenic, and their dynamics related to disease course and disease-modifying treatments.

scholarly journals MAIT cell activation augments adenovirus vector vaccine immunogenicity

Science ◽  
2021 ◽  
Vol 371 (6528) ◽  
pp. 521-526 ◽  
Author(s):  
Nicholas M. Provine ◽  
Ali Amini ◽  
Lucy C. Garner ◽  
Alexandra J. Spencer ◽  
Christina Dold ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cell ◽  
T Cell Responses ◽  
Adjuvant Activity ◽  
Mait Cells ◽  
Cell Responses ◽  
Adenovirus Vectors ◽  
Mait Cell

Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)–derived interferon (IFN)–α and monocyte-derived interleukin-18. IFN-α–induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell–deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.

A subset of follicular helper-like MAIT cells can provide B cell help and support antibody production in the mucosa

2022 ◽  
Vol 7 (67) ◽  
Author(s):  
Owen Jensen ◽  
Shubhanshi Trivedi ◽  
Jeremy D. Meier ◽  
Keke C. Fairfax ◽  
J. Scott Hale ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Production ◽  
Cell Subset ◽  
Mait Cells ◽  
Cell Responses ◽  
Follicular Helper ◽  
B Cell Responses ◽  
Mait Cell

We identify a MAIT cell subset expressing T follicular helper markers and show the ability of MAIT cells to support B cell responses in the mucosa.

scholarly journals B Cells Control Mucosal-Associated Invariant T Cell Responses to Salmonella enterica Serovar Typhi Infection Through the CD85j HLA-G Receptor

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosângela Salerno-Gonçalves ◽  
Tasmia Rezwan ◽  
David Luo ◽  
Hervé Tettelin ◽  
Marcelo B. Sztein
Keyword(s):  
B Cells ◽  
Salmonella Enterica ◽  
Kinetic Studies ◽  
Salmonella Enterica Serovar Typhi ◽  
Mait Cells ◽  
Cell Responses ◽  
Ifn Γ ◽  
And Function ◽  
First Time ◽  
Mait Cell

Mucosal-associated invariant T (MAIT) cells are an innate-like population of T cells that display a TCR Vα7.2+ CD161+ phenotype and are restricted by the nonclassical MHC-related molecule 1 (MR1). Although B cells control MAIT cell development and function, little is known about the mechanisms underlying their interaction(s). Here, we report, for the first time, that during Salmonella enterica serovar Typhi (S. Typhi) infection, HLA-G expression on B cells downregulates IFN-γ production by MAIT cells. In contrast, blocking HLA-G expression on S. Typhi-infected B cells increases IFN-γ production by MAIT cells. After interacting with MAIT cells, kinetic studies show that B cells upregulate HLA-G expression and downregulate the inhibitory HLA-G receptor CD85j on MAIT cells resulting in their loss. These results provide a new role for HLA-G as a negative feedback loop by which B cells control MAIT cell responses to antigens.

scholarly journals Clostridioides difficile Toxin CDT Induces Cytotoxic Responses in Human Mucosal-Associated Invariant T (MAIT) Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Isabel Marquardt ◽  
Josefine Jakob ◽  
Jessica Scheibel ◽  
Julia Danielle Hofmann ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
Cell Activation ◽  
Binary Toxin ◽  
Peripheral Blood Mononuclear ◽  
Host Immune Responses ◽  
Mait Cells ◽  
Cell Responses ◽  
Clostridioides Difficile ◽  
Lytic Granule ◽  
Mait Cell

Clostridioides difficile is the major cause of antibiotic-associated colitis (CDAC) with increasing prevalence in morbidity and mortality. Severity of CDAC has been attributed to hypervirulent C. difficile strains, which in addition to toxin A and B (TcdA, TcdB) produce the binary toxin C. difficile transferase (CDT). However, the link between these toxins and host immune responses as potential drivers of immunopathology are still incompletely understood. Here, we provide first experimental evidence that C. difficile toxins efficiently activate human mucosal-associated invariant T (MAIT) cells. Among the tested toxins, CDT and more specifically, the substrate binding and pore-forming subunit CDTb provoked significant MAIT cell activation resulting in selective MAIT cell degranulation of the lytic granule components perforin and granzyme B. CDT-induced MAIT cell responses required accessory immune cells, and we suggest monocytes as a potential CDT target cell population. Within the peripheral blood mononuclear cell fraction, we found increased IL-18 levels following CDT stimulation and MAIT cell response was indeed partly dependent on this cytokine. Surprisingly, CDT-induced MAIT cell activation was found to be partially MR1-dependent, although bacterial-derived metabolite antigens were absent. However, the role of antigen presentation in this process was not analyzed here and needs to be validated in future studies. Thus, MR1-dependent induction of MAIT cell cytotoxicity might be instrumental for hypervirulent C. difficile to overcome cellular barriers and may contribute to pathophysiology of CDAC.

scholarly journals Monkeying around with MAIT Cells: Studying the Role of MAIT Cells in SIV and Mtb Co-Infection

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 863
Author(s):  
Ryan V. Moriarty ◽  
Amy L. Ellis ◽  
Shelby L. O’Connor
Keyword(s):  
Cell Function ◽  
Current Knowledge ◽  
Cell Activity ◽  
Cell Dynamics ◽  
Tissue Samples ◽  
Mait Cells ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Infected Cells ◽  
Mait Cell

There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control Mycobacterium tuberculosis (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV and TB, knowledge of the immune mechanisms contributing to the loss of control of Mtb replication during HIV infection is lacking. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that target and destroy bacterially-infected cells and may contribute to the control of Mtb infection. Studies examining MAIT cells in human Mtb infection are commonly performed using peripheral blood samples. However, because Mtb infection occurs primarily in lung tissue and lung-associated lymph nodes, these studies may not be fully translatable to the tissues. Additionally, studies longitudinally examining MAIT cell dynamics during HIV/Mtb co-infection are rare, and lung and lymph node tissue samples from HIV+ patients are typically unavailable. Nonhuman primates (NHP) provide a model system to characterize MAIT cell activity during Mtb infection, both in Simian Immunodeficiency Virus (SIV)-infected and SIV-naïve animals. Using NHPs allows for a more comprehensive understanding of tissue-based MAIT cell dynamics during infection with both pathogens. NHP SIV and Mtb infection is similar to human HIV and Mtb infection, and MAIT cells are phenotypically similar in humans and NHPs. Here, we discuss current knowledge surrounding MAIT cells in SIV and Mtb infection, how SIV infection impairs MAIT cell function during Mtb co-infection, and knowledge gaps to address.

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