Gastrointestinal mucosal immunity and COVID-19

Abstract

As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the role of the gut mucosal immune system as a first-line physical and immunological defense is critical. Furthermore, gastrointestinal involvement and symptoms in coronavirus disease 2019 (COVID-19) patients have been linked to worse clinical outcomes. This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection. By carrying out appropriate investigations, the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established. In line with this, COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.

Keywords: COVID-19; Gut microbiota; Gut mucosa; Mucosa; Mucosa-associated lymphoid tissue; SARS-CoV-2; Secretory immunoglobulin A.

Figure 1

Nasal-, bronchial- and mucosa-associated lymphoid tissue are the first line of defense. Airborne infections usually penetrate the upper airway mucosa, where a higher viral load is found. Nasopharynx-associated lymphoid tissue is involved in the induction of the immune response against the microorganisms by promoting the differentiation and activation of immune cells such as Th1- and Th2 cells, dendritic cells, macrophages, resident microfold M cells, innate lymphoid cells, immunoglobulin (Ig)A-switched B cells, as well as immune mediators and molecules (i.e. beta-defensins, galectins, collectins, cytokines). Similar immune processes are also observed in the gut mucosa. However, the expansion of CD4+ T-helper cells, CD8+ cytotoxic T cells, and plasma cells simultaneously with the ongoing innate immune response is critical for virus elimination. Additionally, specific secretory IgA (SIgA) plays an effective role in protection against severe acute respiratory syndrome coronavirus 2 by neutralization, inhibition of adherence, and agglutination. Additionally, SIgA does not activate the classical complement cascade pathway, and thus greater anti- than proinflammatory activity. Innate immune system and some innate receptors (PAMPS, DAMPS) are not shown for simplification of the figure. ACE2: Angiotensin-converting enzyme 2; ARDS: Acute respiratory distress syndrome; BALT: Bronchial-associated lymphoid tissue; GALT: Gut-associated lymphoid tissues; GIT: Gastrointestinal tract. IFN: Interferon; Ig: Immunoglobulin; MALT: Mucosa-associated lymphoid tissue; NALT: Nasopharynx-associated lymphoid tissue; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; TMPRSS2: Transmembrane protease/serine subfamily member 2.