Protective Potentials of Type III Interferons in COVID-19 Patients: Lessons from Differential Properties of Type I- and III Interferons.

While an appropriately regulated production of interferons (IFNs) performs a fundamental role in the defense against coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dysregulated overproduction of inflammatory mediators can play an important role in the development of SARS-CoV-2 infection-related complications, such as acute respiratory distress syndrome. As the principal constituents of innate immunity, both type I and III IFNs share antiviral features. However, important properties, including preferential expression at mucosal barriers (such as respiratory tract), local influences, lower receptor distribution, smaller target cell types, noninflammatory effects, and immunomodulatory impacts, were attributed only to type III IFNs. Accordingly, type III IFNs can establish an optimal effective antiviral response, without triggering exaggerated systemic inflammation that is generally attributed to the type I IFNs. However, some harmful effects were attributed to the III IFNs and there are also major differences between human and mouse concerning the immunomodulatory effects of III IFNs. Here, we describe the differential properties of type I and type III IFNs and present a model of IFN response during SARS-COV-2 infection, while highlighting the superior potential of type III IFNs in COVID-19.

Anti-Leishmanial Vaccines: Assumptions, Approaches, and Annulments.

Leishmaniasis is a neglected protozoan parasitic disease that occurs in 88 countries but a vaccine is unavailable. Vaccination with live, killed, attenuated (physically or genetically) Leishmania have met with limited success, while peptide-, protein-, or DNA-based vaccines showed promise only in animal models. Here, we critically assess several technical issues in vaccination and expectation of a host-protective immune response. Several studies showed that antigen presentation during priming and triggering of the same cells in infected condition are not comparable. Altered proteolytic processing, antigen presentation, protease-susceptible sites, and intracellular expression of pathogenic proteins during Leishmania infection may vary dominant epitope selection, MHC-II/peptide affinity, and may deter the reactivation of desired antigen-specific T cells generated during priming. The robustness of the memory T cells and their functions remains a concern. Presentation of the antigens by Leishmania-infected macrophages to antigen-specific memory T cells may lead to change in the T cells' functional phenotype or anergy or apoptosis. Although cells may be activated, the peptides generated during infection may be different and cross-reactive to the priming peptides. Such altered peptide ligands may lead to suppression of otherwise active antigen-specific T cells. We critically assess these different immunological issues that led to the non-availability of a vaccine for human use.