Pregnant women represent a high-risk population for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The presence of SARS-CoV-2 has been reported in the placenta from infected pregnant women, but whether the virus influences local immune response remains unclear. We showed that the properties of placental macrophages (PMs), isolated from at-term placentas from women infected during the second and third trimesters of pregnancy, exhibited an activated signature associating increased inflammatory markers (NOS2, IDO1, IFNg) and anti-viral markers (type I and III IFN). Activation and recall responses of PMs were also depended on foetal sex. Collectively, these findings reveal that the occurrence of COVID-19 during pregnancy resulted in PM activation, which may provide the basis for protective trained immunity in the case of future reinfection, and may highlight the benefit of vaccination against SARS-CoV-2 for pregnant women.Funding: LG was supported by a Cifre fellowship from ImCheck Therapeutics. SMZ, PAA and AB were supported by the Fondation Méditerranée Infection. This work was supported by the French government under the Investissements d’avenir (Investments for the Future) programme managed by the Agence Nationale de la Recherche (reference number 10-IAHU-03). The “Immunity and Cancer” team was labelled as team FRM DEQ 201 40329534 (for DO). This work was supported by the IMMUNO-COVID project managed by the Agence Nationale de la Recherche Flash COVID (reference IMMUNO-COVID). Declaration of Interest: DO is cofounder and shareholder of ImCheck Therapeutics, Emergence Therapeutics, Alderaan Biotechnology and Stealth IO. The other authors declare that they have no competing interests.Ethical Approval: This prospective observational study was conducted in accordance with the Declaration of Helsinki and the French law on research involving humans. The protocol of the study was approved by an independent national review board (ethics number 08-12) and the clinical study was registered at clinicaltrials.gov (NCT04369859). All pregnant women provided written informed consent. Pregnant women with COVID-19 were recruited at the Gynaecology-Obstetrics Department of the Hôpital de la Conception (Marseille, France) between 15 April 2021 and 31 August 2021.
Vimentin is a type III intermediate filament protein, widely expressed in mesenchymal cells. Mainly located in the cytoplasm, vimentin can also appear at extracellular locations, where it may interact with bacterial or viral pathogens. In this study, we aimed at investigating the implication of vimentin in SARS-CoV-2 viral entry and the consequences on viral replication and cellular response. We showed that upon infection, vimentin was upregulated at the cell surface, where it interacts with ACE2 for SARS-CoV-2 entry. We demonstrated a direct interaction between SARS-CoV-2 spike protein, ACE2, and vimentin in epithelial cells. Inhibition of cell-surface vimentin availability resulted in reduced viral entry and cytopathogenic effects. Finally, we showed that the expression of inflammatory cytokines and chemokines was modulated by vimentin-SARS-CoV-2 interaction. In conclusion, our data suggest that cell-surface vimentin acts as a co-receptor for SARS-CoV-2.
The role of macrophages in viral infections is well documented. Their activation status also called macrophage polarization categorized by the dichotomy of M1 and M2 phenotype remained poorly investigated. Recent studies have shown the complexity of macrophage polarization in response to viral infection and the limits of its use in infected individuals. The aim of this chapter is to reappraise the concept of macrophage polarization in viral infectious diseases, which are more complicated than the models of macrophage-virus interaction. If this concept has been largely used to describe activation status of myeloid cells in experimental conditions, it has to be assessed in light of high-throughput technologies at molecular and phenotypic levels. We update knowledge on macrophage polarization in viral infectious diseases with a special attention for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to coronavirus disease (COVID-19). Hence, we propose an overview of the concept of macrophages as targets for therapeutic intervention in viral infectious disease. Finally, we tempted to focus our approach on patient investigation restricting the use of in vitro experiments and animal models to mechanistic questions.
Abstract Pregnant women represent a high‐risk population for Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) infection. The presence of SARS‐CoV‐2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal–fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID‐19) during their pregnancy. We reported an infiltration of CD163 + macrophages in placenta from COVID‐19 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature ( NOS 2, IDO1 , IFNG , TNF , TGFB ) mainly in women infected during the second trimester of pregnancy. COVID‐19 during pregnancy primed MFM to produce type I and III interferon response to SARS‐CoV‐2 (Wuhan and δ strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID‐19 also primed SARS‐CoV‐2 internalization by MFM in an angiotensin‐converting enzyme 2‐dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS‐CoV‐2 infection, provide a basis for protective placental immunity in COVID‐19, and highlight the interest of vaccination in pregnant women.
Introduction The emergence of several SARS-CoV-2 variants during the COVID pandemic has revealed the impact of variant diversity on viral infectivity and host immune responses. While antibodies and CD8 T cells are essential to clear viral infection, the protective role of innate immunity including macrophages has been recognized. The aims of our study were to compare the infectivity of different SARS-CoV-2 variants in monocyte-derived macrophages (MDM) and to assess their activation profiles and the role of ACE2 (Angiotensin-converting enzyme 2), the main SARS-CoV-2 receptor. We also studied the ability of macrophages infected to affect other immune cells such as γδ2 T cells, another partner of innate immune response to viral infections. Results We showed that the SARS-CoV-2 variants α-B.1.1.7 (United Kingdom), β-B.1.351 (South Africa), γ-P.1 (Brazil), δ-B.1.617 (India) and B.1.1.529 (Omicron), infected MDM without replication, the γ-Brazil variant exhibiting increased infectivity for MDM. No clear polarization profile of SARS-CoV-2 variants-infected MDM was observed. The β-B.1.351 (South Africa) variant induced macrophage activation while B.1.1.529 (Omicron) was rather inhibitory. We observed that SARS-CoV-2 variants modulated ACE2 expression in MDM. In particular, the β-B.1.351 (South Africa) variant induced a higher expression of ACE2, related to MDM activation. Finally, all variants were able to activate γδ2 cells among which γ-P.1 (Brazil) and β-B.1.351 (South Africa) variants were the most efficient. Conclusion Our data show that SARS-CoV-2 variants can infect MDM and modulate their activation, which was correlated with the ACE2 expression. They also affect γδ2 T cell activation. The macrophage response to SARS-CoV-2 variants was stereotypical.
