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Viruses ; 14(1)2022 01 12.
Article in English | MEDLINE | ID: covidwho-1631201


γδ T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of γδ T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human primary γδ T cells have been shown to kill in vitro DENV-infected cells, thus highlighting their possible antiviral function. The aim of this work was to characterize the phenotype and function of Vδ2 T cells in DENV patients. Fifteen DENV patients were enrolled for this study and peripheral blood mononuclear cells (PBMC) were used to analyze Vδ2-T-cell frequency, differentiation profile, activation/exhaustion status, and functionality by multiparametric flow cytometry. Our data demonstrated that DENV infection was able to significantly reduce Vδ2-T-cell frequency and to increase their activation (CD38 and HLA-DR) and exhaustion markers (PD-1 and TIM-3). Furthermore, Vδ2 T cells showed a reduced capability to produce IFN-γ after phosphoantigenic stimulation that can be associated to TIM-3 expression. Several studies are needed to depict the possible clinical impact of γδ-T-cell impairment on disease severity and to define the antiviral and immunoregulatory activities of γδ T cells in the first phases of infection.

Dengue/immunology , Hepatitis A Virus Cellular Receptor 2/metabolism , Interferon-gamma/metabolism , Intraepithelial Lymphocytes/immunology , Adaptation, Physiological , Adult , Flow Cytometry , Hepatitis A Virus Cellular Receptor 2/genetics , Humans , Immunity, Innate , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/immunology , Male , Middle Aged , T-Lymphocyte Subsets/immunology
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240


A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
Signal Transduct Target Ther ; 5(1): 192, 2020 09 07.
Article in English | MEDLINE | ID: covidwho-748172

Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Gene Expression Regulation/immunology , Lymphopenia/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , Biomarkers/blood , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/genetics , Coronavirus Infections/mortality , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/mortality , Disease Progression , Female , Hepatitis A Virus Cellular Receptor 2/blood , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/blood , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Lymphocyte Count , Lymphopenia/diagnosis , Lymphopenia/genetics , Lymphopenia/mortality , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/genetics , Pneumonia, Viral/mortality , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis , T-Lymphocytes/virology , Tumor Necrosis Factor Receptor Superfamily, Member 7/blood , Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 9/blood , Tumor Necrosis Factor Receptor Superfamily, Member 9/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 9/immunology