The seven constitutive respiratory defense barriers against SARS-CoV-2 infection

Abstract

Before eliciting an adaptive immune response, SARS-CoV-2 must overcome seven constitutive respiratory defense barriers. The first is the mucus covering the respiratory tract’s luminal surface, which entraps inhaled particles, including infectious agents, and eliminates them by mucociliary clearance. The second barrier comprises various components present in the airway lining fluid, the surfactants. Besides providing low surface tension that allows efficient gas exchange at the alveoli, surfactants inhibit the invasion of epithelial cells by respiratory viruses, enhance pathogen uptake by phagocytes, and regulate immune cells’ functions. The respiratory tract microbiota constitutes the third defense barrier against SARS-CoV-2. It activates the innate and adaptive immune cells and elicits anti-infectious molecules such as secretory IgA antibodies, defensins, and interferons. The fourth defense barrier comprises the antimicrobial peptides defensins, and lactoferrin. They show direct antiviral activity, inhibit viral fusion, and modulate the innate and adaptive immune responses. Secretory IgA antibodies, the fifth defense barrier, besides protecting the local microbiota against noxious agents, also inhibit SARS-CoV-2 cell invasion. If the virus overcomes this barrier, it reaches its target, the respiratory epithelial cells. However, these cells also act as a defense barrier, the sixth one, since they hinder the virus’ access to receptors and produce antiviral and immunomodulatory molecules such as interferons, lactoferrin, and defensins. Finally, the sensing of the virus by the cells of innate immunity, the last constitutive defense barrier, elicits a cascade of signals that activate adaptive immune cells and may inhibit the development of productive infection. The subject of the present essay is discussing these mechanisms.

Progress in salivary glands: Endocrine glands with immune functions

“…Human MUC19 transcripts in salivary glands (n = 7) and MUC19 glycoproteins in glandular mucous cells and saliva are also found (69). Mucosal immunity including the mucus covering the respiratory tract, surfactants, anti-infectious molecules (sIgA, defensins, and interferons), respiratory epithelial cells, and innate immunity cells (nasal goblet cells and macrophages), form a mucosal barrier that plays a vital role in COVID-19 (70). The mucosal immune system in the nasal and oral cavities, acts as the first barrier, with the appearance of sIgA in the saliva (4).…”

The Role of the Gut-Lung Axis in COVID-19 Infections and Its Modulation to Improve Clinical Outcomes

“…In addition, IgA can neutralize extra-and intracellular pathobiont toxins as it can bind a wide range of antigens due to their low affinity. IgA antibodies can bind to lipopolysaccharides (LPS), DNAs, flagellin, capsular polysaccharides and viral components [3,39]; and can eliminate pathogens or antigens via an IgA-mediated excretory pathway that binding to IgA progresses poly-immunoglobulin receptor mediated transport of immune complexes [40]. Epithelial cells infected viruses secrete a broad range of interferons and as such can have direct immune effects and confer resistance to uninfected cells [41].…”

“…The shedding of virus particles in the cell debris are then inhaled into the lung. In the lung, the virus can enter the systemic circulation with ease due to high mucosal permeability [3,4]. It has also been demonstrated that the oral cavity is also an important site for the replication of the SARS-CoV-2 virus [5].…”

Surfactant therapy for pneumonia COVID-19 of obstetric patients

“…Помимо обеспечения низкого поверхностного натяжения, обеспечиваю щего эффективный газообмен в альвеолах, сурфактантная система легких обладает способностью предотвращать непосредственное воздействие вируса на клетку за счет возможности сорбировать на своей поверхности вирусы и бактерии с последующим предоставлением их альвеолярным макрофагам [21,22]. Кроме того, при дефиците легочного сурфактанта из-за уменьшения продольного градиента поверхностного давления нарушается перемещение мокроты в зону мукоцилиарного транспорта, что препятcтвует санации альвеол и нижних дыхательных путей [12,14].…”