Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection
Nurhan Albayrak, Carmen Orte Cano, Sina Karimi, David Dogahe, Anne Van Praet, Audrey Godefroid, V. del Mármol, David Grimaldi, Benjamin Bondue, Jean‐Paul Van Vooren, Françoise Mascart, Véronique Corbière
Abstract
The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1 + classical, intermediate, and non-classical monocytes and the proportions of IL-22R1 + plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1 + classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1 + non-classical monocytes and mDC2 displayed HLA-DR high expression and were thus activated. Multivariate analysis for all IL-22R1 + myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1 + cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1 + classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1 + intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4 + T cells produced IFN-γ and IL-22, and CD4 + and CD8 + T cells produced IL-17A. CD4 + T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4 + T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time.