Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
Sci Rep ; 11(1): 14090, 2021 07 08.
Article in English | MEDLINE | ID: covidwho-1303787

ABSTRACT

MAIT cells have been shown to be activated upon several viral infections in a TCR-independent manner by responding to inflammatory cytokines secreted by antigen-presenting cells. Recently, a few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. In this study, we investigate the effect of SARS-CoV-2 infection on the frequency and phenotype of MAIT cells by flow cytometry, and we test in vitro stimulation conditions on the capacity to enhance or rescue the antiviral function of MAIT cells from patients with coronavirus disease 2019 (COVID-19). Our study, in agreement with recently published studies, confirmed the decline in MAIT cell frequency of hospitalized donors in comparison to healthy donors. MAIT cells of COVID-19 patients also had lower expression levels of TNF-alpha, perforin and granzyme B upon stimulation with IL-12 + IL-18. 24 h' incubation with IL-7 successfully restored perforin expression levels in COVID-19 patients. Combined, our findings support the growing evidence that SARS-CoV-2 is dysregulating MAIT cells and that IL-7 treatment might improve their function, rendering them more effective in protecting the body against the virus.


Subject(s)
COVID-19/prevention & control , COVID-19/virology , Interleukin-7/pharmacology , Mucosal-Associated Invariant T Cells/physiology , Mucosal-Associated Invariant T Cells/virology , SARS-CoV-2/pathogenicity , Cells, Cultured , Female , Granzymes/metabolism , Humans , Male , Mucosal-Associated Invariant T Cells/metabolism , Perforin/metabolism , Tumor Necrosis Factor-alpha/metabolism
2.
Mol Immunol ; 130: 154-158, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065484

ABSTRACT

Mucosal associated invariant T (MAIT) cells have a recognised innate-like capacity for antibacterial host defence, consequent on the specificity of their T cell receptor (TCR) for small molecule metabolites produced by a range of prokaryotic and fungal species, their effector memory phenotype, and their expression of cytotoxic molecules. However, recent studies have identified at least two other important functions of MAIT cells in antiviral immunity and in tissue homeostasis and repair. Each are related to distinct transcriptional programmes, which are activated differentially according to the specific immune context. Here we discuss these diverse functions, we review the evidence for the newly identified role of MAIT cells in promoting tissue repair, and we discuss emerging data pointing to the future directions of MAIT cell research including roles in cancer, in antiviral immunity and recent studies in the immune response to SARS-CoV-2 infection. Overall these studies have made us aware of the potential for pleiotropic roles of MAIT cells and related cell populations in micee and humans, and have created a simple and attractive new paradigm for regulation in barrier tissues, where antigen and tissue damage are sensed, integrated and interpreted.


Subject(s)
Mucosal-Associated Invariant T Cells/immunology , Animals , Bacterial Infections/immunology , Homeostasis , Humans , Mucosal-Associated Invariant T Cells/cytology , Mucosal-Associated Invariant T Cells/metabolism , Neoplasms/immunology , Receptors, Antigen, T-Cell , Virus Diseases/immunology
3.
Viruses ; 13(2)2021 02 03.
Article in English | MEDLINE | ID: covidwho-1060774

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.


Subject(s)
COVID-19/immunology , Lymphocyte Activation , Mucosal-Associated Invariant T Cells/immunology , Adaptive Immunity , COVID-19/physiopathology , Cytokines/metabolism , Female , Granzymes/metabolism , HLA-DR Antigens , Humans , Interleukin-17/metabolism , Killer Cells, Natural/immunology , Male , Mucosal-Associated Invariant T Cells/metabolism , Severity of Illness Index , T-Lymphocyte Subsets/immunology , Tumor Necrosis Factor-alpha/metabolism
4.
J Exp Med ; 217(12)2020 12 07.
Article in English | MEDLINE | ID: covidwho-744478

ABSTRACT

COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS-CoV-2-driven ARDS.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/immunology , Mucosal-Associated Invariant T Cells/metabolism , Natural Killer T-Cells/metabolism , Phenotype , Pneumonia, Viral/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Respiratory Distress Syndrome/immunology , Aged , Antigens, CD/blood , Antigens, Differentiation, T-Lymphocyte/blood , COVID-19 , Cells, Cultured , Coronavirus Infections/virology , Cytokines/metabolism , Female , Humans , Inflammation/immunology , Inflammation/metabolism , Lectins, C-Type/blood , Male , Middle Aged , Mucosal-Associated Invariant T Cells/immunology , Natural Killer T-Cells/immunology , Pandemics , Pneumonia, Viral/virology , Prognosis , Prospective Studies , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Severity of Illness Index
5.
Crit Rev Immunol ; 40(2): 173-184, 2020.
Article in English | MEDLINE | ID: covidwho-663846

ABSTRACT

Mucosa-associated invariant T cells (MAIT cells) are unconventional, innate-like T lymphocytes with remarkable effector and immunoregulatory functions. They are abundant in the human peripheral blood and also enriched in mucosal layers and in the lungs, SARS-CoV-2's main ports of entry. Once activated, MAIT cells produce inflammatory cytokines and cytolytic effector molecules quickly and copiously. MAIT cells are best known for their antibacterial and antifungal properties. However, they are also activated during viral infections, typically in a cytokine-dependent manner, which may promote antiviral immunity. On the other hand, it is plausible to assume active roles for MAIT cells in infection-provoked cytokine storms and tissue damage. SARS-CoV-2 infection may be asymptomatic, mild, severe, or even fatal, depending on sex, age, the presence of preexisting morbidities, and the individual's immunological competence, or lack thereof, among other factors. Based on the available literature, I propose that MAIT cells regulate the host response to SARS-CoV-2 and constitute attractive targets in the prevention or clinical management of coronavirus disease 19 (COVID-19) and some of its complications. Unlike mainstream T cells, MAIT cells are restricted by a monomorphic antigen-presenting molecule called MHC-related protein 1 (MR1). Therefore, MR1 ligands should modify MAIT cell functions relatively uniformly in genetically diverse subjects and may be tested as immunotherapeutic agents or vaccine adjuvants in future studies.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Histocompatibility Antigens Class I/metabolism , Minor Histocompatibility Antigens/metabolism , Mucosal-Associated Invariant T Cells/immunology , Pneumonia, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Coronavirus Infections/pathology , Cytokines/immunology , Humans , Mucosal-Associated Invariant T Cells/metabolism , Pandemics , Pneumonia, Viral/pathology , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL