Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral‐ or bacterial‐oriented immune responses

Abstract

Introduction: CD64 expression increases on neutrophils during bacterial infections. Recently an increase in CD169 expression has been discovered on monocytes during viral infections. Generally, interferons α (IFNsα) andIFNsγ are key drivers of the infectious host immune response. The purpose of this study was to explore if a link exists between these IFNs and both biomarkers. Methods: Whole blood samples from healthy volunteers were stimulated with either IFNs, interleukins, or infectious extracts, to mimic an infectious state. Expressions of CD64 and CD169 were assessed in these samples by multiple flow cytometry methods, over precise kinetics.Results: The expression of CD64 was statistically higher in samples stimulated with IFNγ, and CD169 in those stimulated with IFNα (and all other type I IFNs).Surface expressions are directly induced by their respective IFNs via Janus kinase/ signal transducer and activator of transduction pathways within 6 to 8 hours of incubation. Mixing both types of IFNs seemed to indicate that they partially inhibit each other. Conclusions: The induction of CD169 on monocytes and CD164 on neutrophils by type I and type II IFNs confirms the relevance of these markers for assessing between a viral-vs bacterial-oriented immune response.

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

“…Unbiased analysis by Uniform Manifold Approximation and Projection (UMAP) and graph-based clustering however identified with CD169 + monocytes and CD11b high neutrophils, two additional clusters with high variation in acute patients (Figure 1C). Further analysis showed that the monocytes presented with an increased expression of CD169 (strong type I interferon signature marker 14 ), increased expression of CD11b and HLA-DR, as well as CD33, a constitutive PI3K signaling inhibitor 15,16 (Figure 1D, Supplementary Figure 1B).…”

CD64 and CD169 could help differentiate bacterial from viral infections in Emergency Department

“…CD64 on neutrophils and CD169 on monocytes were the two main biomarkers assessed in this study by flow cytometry for discriminating between bacterial versus viral infections. Expressions of these two biomarkers have been shown to be directly induced, within hours, by interferons produced by the body in response to pathogen detection (14). Ability of nCD64 to discriminate between bacterial and non-bacterial infections has been largely demonstrated for years (17), whereas mCD169 increase after infection by viruses has only been described recently.…”

“…We developed a rapid flow cytometry assay, able to measure leucocytes biomarkers expressions within 10 minutes (12), and demonstrated promising results for the triage of patients with fever at the Emergency Department (13,14), with CD64 on neutrophils (nCD64), increased in case of bacterial infections (15), and CD169 on monocytes (mCD169), increased in case of viral infections (16). In these previous studies, one limitation was the low number of infected patients, especially those with viral diseases.…”

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

“…1c). Further analysis showed that the monocytes presented with an increased expression of CD169 (strong type I interferon signature marker 16 ), increased expression of CD11b and HLA-DR, as well as CD33, a constitutive PI3K signalling inhibitor 17,18 (Fig. 1d, Supplementary Fig.…”