Abstract
In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed to evaluate the immunomodulatory effects of D. pigrum 040417 in human respiratory epithelial cells and the potential ability of this immunobiotic bacterium to increase the protection against Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The respiratory commensal bacterium D. pigrum 040417 differentially modulated the production of IFN-β, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of Calu-3 cells stimulated with poly(I:C) or challenged with SARS-CoV-2. The differential cytokine profile induced by the 040417 strain was associated with a significant reduction in viral replication and cellular damage after coronavirus infection. Of note, D. pigrum 030918 was not able to modify the resistance of Calu-3 cells to SARS-CoV-2 infection, indicating a strain-specific immunomodulatory effect for respiratory commensal bacteria. The findings of this work improve our understanding of the immunological mechanisms involved in the modulation of respiratory immunity induced by respiratory commensal bacteria, by demonstrating their specific effect on respiratory epithelial cells. In addition, the results suggest that particular strains such as D. pigrum 040417 could be used as a promising alternative for combating SARS-CoV-2 and reducing the severity of COVID-19.
Highlights
Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 19 (COVID-19) pandemic
It was observed that the reduced production of IFN-β in patients with COVID-19 is accompanied by elevated secretion of interleukin (IL)-6, chemokine (C-C motif) ligand 2 (CCL2), CCL5, CCL8, chemokine (C-X-C motif) ligand 8 (CXCL8), CXCL9, CXCL16, and CXCL2, which contribute to aggravating COVID-19 pathology [7,8] through the recruitment of inflammatory monocytes and neutrophils into the respiratory tract [6]
In order to evaluate whether the enhanced resistance of respiratory epithelial cells to SARS-CoV-2 challenge was associated with a different cytokine profile, we further evaluated the concentrations of IFN-β, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of infected cells (Figure 3)
Summary
Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 19 (COVID-19) pandemic. It was shown that in addition to the cytopathic effect induced by the virus, the respiratory alterations caused by SARS-CoV-2 are mediated by an aggressive inflammatory response that significantly contributes to damage in the respiratory tissues. It was reported that the replication of SARS-CoV-2 induces extensive death in epithelial cells, and causes the release of pro-inflammatory cytokines/chemokines and the recruitment of inflammatory cells into the respiratory tract [6]. It was observed that the reduced production of IFN-β in patients with COVID-19 is accompanied by elevated secretion of interleukin (IL)-6, chemokine (C-C motif) ligand 2 (CCL2), CCL5, CCL8, chemokine (C-X-C motif) ligand 8 (CXCL8), CXCL9, CXCL16, and CXCL2, which contribute to aggravating COVID-19 pathology [7,8] through the recruitment of inflammatory monocytes and neutrophils into the respiratory tract [6]
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