With the worldwide spread of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, ...the SARS‐CoV‐2‐induced coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies.
In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome–related coronavirus 2 (SARS‐CoV‐2), has ...developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19–related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.
Background
Cannabinoids are lipid‐derived mediators with anti‐inflammatory properties in different diseases. WIN55212‐2, a non‐selective synthetic cannabinoid, reduces immediate anaphylactic ...reactions in a mouse model of peanut allergy, but its capacity to prevent peanut‐allergic sensitization and the underlying mechanisms remains largely unknown.
Objective
To investigate the capacity of WIN55212‐2 to immunomodulate peanut‐stimulated human dendritic cells (DCs) and peanut‐allergic sensitization in mice.
Methods
Surface markers and cytokines were quantified by flow cytometry, ELISA and qPCR in human monocyte‐derived DCs (hmoDCs) and T‐cell cocultures after stimulation with peanut alone or in the presence of WIN55212‐2. Mice were epicutaneously sensitized with peanut alone or peanut/WIN55212‐2. After peanut challenge, drop in body temperature, haematocrit, clinical symptoms, peanut‐specific antibodies in serum and FOXP3+ regulatory (Treg) cells in spleen and lymph nodes were quantified. Splenocytes were stimulated in vitro with peanut to analyse allergen‐specific T‐cell responses.
Results
WIN55212‐2 reduced peanut‐induced hmoDC activation and promoted the generation of CD4+CD127−CD25+FOXP3+ Treg cells, while reducing the induction of IL‐5‐producing T cells. In vivo, WIN55212‐2 impaired the peanut‐induced migration of DCs to lymph nodes and their maturation. WIN55212‐2 significantly reduced the induction of peanut‐specific IgE and IgG1 antibodies in serum during epicutaneous peanut sensitization, reduced the clinical symptoms score upon peanut challenge and promoted the generation of allergen‐specific FOXP3+ Treg cells.
Conclusions
The synthetic cannabinoid WIN55212‐2 interferes with peanut sensitization and promotes tolerogenic responses, which might well pave the way for the development of novel prophylactic and therapeutic strategies for peanut allergy.
Peanut allergy represents the most common cause of food‐induced anaphylaxis. We show that the synthetic cannabinoid WIN55212‐2 reduces peanut‐induced human dendritic cell maturation and promotes the generation of regulatory T cells (Tregs), while reducing IL‐5‐producing T cells. In vivo, the administration of WIN55212‐2 during epicutaneous peanut sensitization in mice decreases the induction of peanut‐specific IgE and IgG1 antibodies in serum and promotes the generation of allergen‐specific FOXP3+ Tregs. Our data indicate that WIN55212‐2 interferes with peanut sensitization promoting tolerogenic responses.
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