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Cells ; 10(5)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1274611


Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host's immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage.

Myocarditis/immunology , Th17 Cells/metabolism , Virus Diseases/immunology , Adenoviridae , Animals , Autoimmune Diseases/immunology , Chikungunya virus , Cytokines/immunology , Dengue Virus , Humans , Immune System , Immunosuppressive Agents/pharmacology , Inflammation , Interleukin-10/biosynthesis , Lymphocytes/cytology , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/virology , Myocarditis/metabolism , Myocarditis/virology , Orthomyxoviridae , SARS-CoV-2 , Simplexvirus , Th1 Cells/cytology , Th2 Cells/cytology , Virus Diseases/drug therapy , Virus Diseases/metabolism , Zika Virus
Int J Radiat Oncol Biol Phys ; 110(5): 1283-1294, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1129036


PURPOSE: Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown. METHODS AND MATERIALS: Here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and toll-like receptor (TLR)-3 stimulation in human lung macrophages. RESULTS: Low doses of RT (0.5-1 Gray) decreased LPS-induced pneumonia, and increased the percentage of nerve- and airway-associated macrophages producing interleukin (IL) 10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses of RT increased IL-10 production by infiltrating immune cells into the lung. Irradiation of TLR-3 ligand-stimulated human lung macrophages ex vivo increased IL-10 secretion and decreased interferon γ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased. CONCLUSIONS: Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.

Epithelial Cells/radiation effects , Influenza A Virus, H1N1 Subtype , Interleukin-10/biosynthesis , Macrophages/radiation effects , Pneumonia, Viral/radiotherapy , Respiratory Distress Syndrome/radiotherapy , Animals , Anti-Inflammatory Agents/pharmacology , COVID-19/complications , Dexamethasone/pharmacology , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/metabolism , Female , Flow Cytometry , Humans , Influenza A Virus, H1N1 Subtype/radiation effects , Interferon-gamma/biosynthesis , Interleukin-6/biosynthesis , Lipopolysaccharides , Lung/cytology , Lung/pathology , Lung/radiation effects , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Pneumonia, Viral/etiology , Pneumonia, Viral/prevention & control , Poly I-C , Radiotherapy Dosage , Respiratory Distress Syndrome/etiology , Toll-Like Receptor 3 , Viral Load/radiation effects
Expert Rev Mol Diagn ; 20(11): 1087-1097, 2020 11.
Article in English | MEDLINE | ID: covidwho-800633


INTRODUCTION: Coronavirus disease (COVID-19) can trigger a cytokine response storm (CRS) that is associated with high mortality but for which the underlying pathophysiology and diagnostics are not yet well characterized. This review provides an overview of the underlying immune profile of COVID-19-related CRS as well as laboratory markers for acute diagnosis and chronic follow-up of patients with SARS-CoV-2 and CRS. AREAS COVERED: Innate and acquired immune profiles in COVID-19-CRS, RNA-detection methods for SARS-CoV-2 in the setting of CRS including factors that affect assay performance, serology for SARS-CoV-2 in the setting of CRS, and other biomarkers for COVID-19 will be discussed. EXPERT OPINION: Studies support the implication of CRS in the pathogenesis, clinical severity and outcome of COVID-19 through the production of multiple inflammatory cytokines and chemokines from activated innate and adaptive immune cells. Although these inflammatory molecules, including IL-6, IL-2 R, IL-10, IP-10 and MCP-1, often correlate with disease severity as possible biomarkers, the pathogenic contributions of individual molecules and the therapeutic benefits of targeting them are yet to be demonstrated. Detection of SARS-CoV-2 RNA is the gold standard method for diagnosis of COVID-19 in the context of CRS but assay performance varies and is susceptible to false-negative results even as patients clinically deteriorate due to decreased viral shedding in the setting of CRS. Biomarkers including CRP, ferritin, D-dimer and procalcitonin may provide early clues about progression to CRS and help identify thrombotic and infectious complications of COVID-19.

Biomarkers/blood , COVID-19/blood , Cytokine Release Syndrome/blood , Cytokines/blood , Adaptive Immunity/immunology , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Chemokine CCL2/biosynthesis , Chemokine CCL2/immunology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Cytokines/biosynthesis , Cytokines/immunology , Humans , Immunity, Innate/immunology , Interleukin-10/biosynthesis , Interleukin-10/immunology , Interleukin-6/biosynthesis , Interleukin-6/immunology , Pandemics , Receptors, Interleukin-2/biosynthesis , Receptors, Interleukin-2/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index