Jiri Mestecky

Secretory (S) IgA antibodies against severe acute respiratory syndrome (SARS)-CoV-2 are induced in saliva and upper respiratory tract (URT) secretions by natural infection and may be critical in determining the outcome of initial infection. Secretory IgA1 (SIgA1) is the predominant isotype of antibodies in these secretions. Neutralization of SARS-CoV-2 is most effectively accomplished by polymeric antibodies such as SIgA. We hypothesize that cleavage of SIgA1 antibodies against SARS-CoV-2 by unique bacterial IgA1 proteases to univalent Fabα antibody fragments with diminished virus neutralizing activity would facilitate the descent of the virus into the lungs to cause serious disease and also enhance its airborne transmission to others. Recent studies of the nasopharyngeal microbiota of patients with SARS-CoV-2 infection have revealed significant increases in the proportions of IgA1 protease-producing bacteria in comparison with healthy subjects. Similar considerations might apply also to other respiratory viral infections including influenza, possibly explaining the original attribution of influenza to Haemophilus influenzae , which produces IgA1 protease.

The early demonstration of the presence of antibodies in external secretions of the gastrointestinal tract and later in milk, saliva, tears, respiratory and genital tract secretions, and urine stimulated extensive studies of their structure, function, and induction following immunization. In contrast to plasma, external secretions contain lower levels and a markedly different immunoglobulin (Ig) isotype distribution of antibodies with characteristic structural and functional properties. Igs of all isotypes are present in external secretions; however, their relative distribution and molecular forms display marked differences in comparison with plasma. All isotypes of Igs are present in external secretions, albeit at markedly different concentrations. The transport of polymeric Igs across mucosal epithelial cells is mediated by a transmembrane glycoprotein called the polymeric Igreceptor. In humans and several other species, the production of IgA far exceeds the combined synthesis of all other isotypes of Igs. Humans and other primates have evolved a distinct pathway for transport of secretory antibodies into bile.

Background:Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT).Methods: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103+CD69+ CD4+ and CD8+ T cells in mucosa-derived T cells from healthy and HIV-positive women.Results: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women. The expression of the mucosal retention receptor, CD103, from HIV-positive women was reduced compared to healthy women and was lowest in women with CD4 counts < 500 cells/mm3. Furthermore, CD103 expression on mucosa-derived CD8+ T cells correlated with antigen-specific IFN-γ production by mucosal CD4+ T cells and was inversely correlated with T-bet from CD8+CD103+ mucosa-derived T cells.Conclusions: These data suggest that CD4+ T cells, known to be impaired during HIV-1 infection and necessary for the expression of CD103 in murine models, may play a role in the expression of CD103 on resident T cells from the human FGT.