Immune regulation of AP-N, DDP4 and ACE2 receptors and the susceptibility to infections with coronavirus 229E, MERS-CoV and SARS-CoV2

ABSTRACT

The Coronaviridae family includes the seven known human coronavi-ruses (HCoV) that cause mild to moderate respiratory infections (HCo-V-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) as well as severe illness and death (MERS-CoV, SARS-CoV, SARS-CoV-2). Severe infections in-duce inflammatory responses that are often intensified by host ada-ptive immune pathways. Proinflammatory responses are triggered by CoV entry mediated by host cell surface receptors. Interestingly, four of the seven strains use cell surface metallopeptidases as receptors. The entry receptors for specific coronaviruses are aminopeptidase N (AP-N), dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme 2 (ACE2) for HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV2, respectively. In addition, these receptors perform many physiological functions, including the regulation of the circulatory and immune sys-tems. Coronavirus receptors are also highly expressed in human tissues and organs (intestines, kidneys, heart, lungs). Additionally, some cy-tokines, chemokines, and other proteins and immune cells influence the modulation of the expression of coronavirus receptors. This review presents the biological role of receptor proteins in the regulation of human physiological systems, the impact of the immune response on susceptibility to coronavirus infections, and the potential effects of glucocorticosteroids (GCS) and specific allergen immunotherapy (AIT) used in the treatment of asthma and allergy on the suscpetibility to coronaviral infections.