1. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract.
- Author
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Alosaimi B, Hamed ME, Naeem A, Alsharef AA, AlQahtani SY, AlDosari KM, Alamri AA, Al-Eisa K, Khojah T, Assiri AM, and Enani MA
- Subjects
- Adult, Aged, Aged, 80 and over, Bronchi immunology, Bronchi pathology, Bronchi virology, Coronavirus Infections mortality, Cytokines genetics, Cytokines immunology, Down-Regulation genetics, Down-Regulation immunology, Female, Humans, Immunity, Innate genetics, Immunity, Innate immunology, Inflammation genetics, Inflammation immunology, Male, Middle Aged, Viral Load, Virus Replication immunology, Coronavirus Infections immunology, Coronavirus Infections pathology, Cytokines blood, Middle East Respiratory Syndrome Coronavirus immunology, Th1 Cells immunology, Th2 Cells immunology
- Abstract
MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4
+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.) more...- Published
- 2020
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