Abstract

Basophils play a key role in the orientation of immune responses. Though the interaction of SARS-CoV-2 with various immune cells has been relatively well studied, the response of basophils to this pandemic virus is not characterized yet. In this study, we report that SARS-CoV-2 induces cytokine responses and in particular IL-13, in both resting and IL-3 primed basophils. The response was prominent under IL-3 primed condition. However, either SARS-CoV-2 or SARS-CoV-2-infected epithelial cells did not alter the expression of surface markers associated with the activation of basophils, such as CD69, CD13 and/or degranulation marker CD107a. We also validate that human basophils are not permissive to SARS-CoV-2 replication. Though increased expression of immune checkpoint molecule PD-L1 has been reported on the basophils from COVID-19 patients, we observed that SARS-CoV-2 does not induce PD-L1 on the basophils. Our data suggest that basophil cytokine responses to SARS-CoV-2 might help in reducing the inflammation and also to promote antibody responses to the virus.

Highlights

  • The current COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an unprecedented danger to global health systems, with over 5.2 million confirmed fatalities (10th December 2021) [1]

  • We found that SARS-CoV-2 induces IL-4 and IL-13 cytokines both in resting and IL-3primed basophils without modifying the expression of surface markers including the checkpoint molecule PD-L1

  • Though the phenotype of basophils was previously analyzed in COVID-19 patients [11], it was not clear whether the activated basophil phenotype observed in the COVID-19 patients was due to direct virus stimulation or a repercussion of inflammatory responses

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Summary

Introduction

The current COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an unprecedented danger to global health systems, with over 5.2 million confirmed fatalities (10th December 2021) [1]. Large number of studies have dissected the spectrum of innate and adaptive immune responses in COVID-19 patients and their role in the immunopathogenesis of the disease [2–7]. In addition to mediating the protection against helminth infection, basophils are well known for their role in the pathogenesis of various allergic inflammatory diseases of respiratory tract, gastro-intestinal tract and skin [8–10]. A longitudinal systems-level analyses of immune cells from the blood indicates that basophils are depleted during acute and severe phases of COVID-19 [2] and in line with the established fact that basophils regulate T and B cell responses, a correlation between anti-RBD (receptor-binding domain) IgG titers and basophil number in the circulation has been observed [2]. The direct response of human basophils to SARS-CoV-2 remains unexplored

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