Background: Coronavirus disease 2019 (COVID-19) clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during COVID-19 and if monocytes and macrophages could be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Monocytes and monocyte-derived macrophages (MDMs) from COVID-19 patients and controls were infected with SARS-CoV-2 and extensively investigated with immunofluorescence, viral RNA extraction and quantification, and total RNA extraction followed by reverse-transcription quantitative polymerase chain reaction using specific primers, supernatant cytokines (interleukins 6, 10, and 1β; interferon-β; transforming growth factor–β1, and tumor necrosis factor–α), and flow cytometry. The effect of M1- vs M2-type or no polarization prior to infection was assessed. Results: SARS-CoV-2 efficiently infected monocytes and MDMs, but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In COVID-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity. Conclusions: SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of COVID-19 progression. SARS-CoV-2 infection of macrophages induces a specific M2 transcriptional program. In Covid-19 patients, monocyte subsets were decreased associated with up-expression of the immunoregulatory molecule CD163 suggesting that SARS-CoV-2 drives immune system for the benefit of Covid-19 disease progression.

An unbiased approach of SARS-CoV-2-induced immune dysregulation has not been undertaken so far. We aimed to identify previously unreported immune markers able to discriminate COVID-19 patients from healthy controls and to predict mild and severe disease. An observational, prospective, multicentric study was conducted in patients with confirmed COVID-19: mild/moderate (n=7) and severe (n=19). Immunophenotyping of whole blood leukocytes was performed in patients upon hospital ward or intensive care unit admission and in healthy controls (n=25). Clinically relevant associations were identified through unsupervised analysis. Granulocytic (neutrophil, eosinophil and basophil) markers were enriched during COVID-19 and discriminated between mild and severe patients. Increased counts of CD15 ⁺CD16 ⁺ neutrophils, decreased granulocytic expression of integrin CD11b, and Th2-related CRTH2 downregulation in eosinophils and basophils established a COVID-19 signature. Severity was associated with the emergence of PDL1 checkpoint expression in basophils and eosinophils. This granulocytic signature was accompanied by monocyte and lymphocyte immunoparalysis. Correlation with validated clinical scores supported pathophysiological relevance. Phenotypic markers of circulating granulocytes are strong discriminators between infected and uninfected individuals as well as between severity stages. COVID-19 alters the frequency and functional phenotypes of granulocyte subsets with the emergence of CRTH2 as a disease biomarker.

IgE-mediated type I hypersensitivity reactions have many reported beneficial functions in immune defense against parasites, venoms, toxins, etc. However, they are best known for their role in allergies, currently affecting almost one third of the population worldwide. IgE-mediated allergic diseases result from a maladaptive type 2 immune response that promotes the synthesis of IgE antibodies directed at a special class of antigens called allergens. IgE antibodies bind to type I high-affinity IgE receptors (FcεRI) on mast cells and basophils, sensitizing them to get triggered in a subsequent encounter with the cognate allergen. This promotes the release of a large variety of inflammatory mediators including histamine responsible for the symptoms of immediate hypersensitivity. The development of type 2-driven allergies is dependent on a complex interplay of genetic and environmental factors at barrier surfaces including the host microbiome that builds up during early life. While IgE-mediated immediate hypersensitivity reactions are undoubtedly at the origin of the majority of allergies, it has become clear that similar responses and symptoms can be triggered by other types of adaptive immune responses mediated via IgG or complement involving other immune cells and mediators. Likewise, various nonadaptive innate triggers via receptors expressed on mast cells have been found to either directly launch a hypersensitivity reaction and/or to amplify existing IgE-mediated responses. This review summarizes recent findings on both IgE-dependent and IgE-independent mechanisms in the development of allergic hypersensitivities and provides an update on the diagnosis of allergy.

There is much interest in predicting and controlling the outcome of interaction between artificial surfaces and living cells. However, although there is an impressive amount of information on the behaviour of many cell populations deposited on a variety of surfaces, there is presently no available theory to explain or even summarize these data. Indeed, it is not even obvious that such a theory may exist. The aim of the present review is to emphasize the problems encountered when one attempts to build such a theory. Three sequential steps of cell surface interactions are considered: 1) protein adsorption is a preliminary step liable to involve irreversible interaction between the surface and several hundreds of molecular species occurring in blood or plasma. 2) the second step is the formation of adhesive bonds. Several theoretical frameworks were suggested to account for this step, including DLVO theory, physical chemistry of surfaces, and formation of specific ligand-receptor bonds. It is concluded that present evidence supports the latter approach, although this involves serious difficulties. 3) The last step is the triggering of a specific cell program such as apoptosis, proliferation, migration, differentiation or activation. Recent evidence suggests that in addition to the nature and amount of stimulated surface receptors, additional cues such as substratum mechanical or topographical properties may significantly affect cell behaviour.

Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators – stored in granules – as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.