Lessons Learned from SARS-CoV and MERS-CoV: Preparation for SARS-CoV-2 induced COVID-19

Coronaviruses (CoVs) are the largest positive-sense RNA viruses with a wide range of natural hosts. To date, seven types of coronaviruses (HCoV-NL63; Human coronavirus NL63, HCoV-229E; Human coronavirus 229E, HCoV-OC43; Human coronavirus OC43, HCoV-HKU1; Human coronavirus HKU1, SARS-CoV; Severe acute respiratory syndrome-related coronavirus, MERS-Co; Middle East respiratory syndrome coronavirus, and SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus) are known to cause disease in humans, and three of the CoVs (SARS-CoV, MERS-CoV, and SARS-CoV-2) cause severe, occasionally fatal, respiratory infections in humans. In November 2002, the case of severe acute respiratory syndrome (SARS), a new respiratory illness caused by SARS-CoV, was first reported in Guangdong Province, China. For the next several months, the SARS outbreak resulted in more than 8,000 cases of infection and 800 deaths. In June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia with 2,373 reported viral infections and 823 associated deaths until February 2019. The outbreak of the MERS-CoV pandemic also occurred in South Korea in May 2015. In late December 2019, another novel coronavirus called SARS-CoV-2, genetically linked to SARS-CoV, emerged in Wuhan, Hubei Province of China that has spread worldwide. Outbreaks of coronavirus-infections are occurring frequently in the 21st century; therefore, it seems very likely that another pandemic of coronavirus can emerge anytime in the future. In this review, we outlined the biological characteristics of coronaviruses and summarized the status of vaccine development against SARS-CoV-2, SARS-CoV, and MERS-CoV in preparation for the unpredictable emergence of coronavirus pandemic.

Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes into Macrophage-like Cells via the MAPK Signaling Pathway

Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal tract of animals. Although intensive functional studies have been done for other galectin isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic changes on monocytes by altering the expression of various surface molecules, and induced functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity. Concomitant with these changes, Gal-4-treated monocytes became adherent and showed elongated morphology with higher expression of macrophage markers. Notably, we found that Gal-4 interacted with CD14 and activated the MAPK signaling cascade. Therefore, these findings suggest that Gal-4 may exert the immunoregulatory functions through the activation and differentiation of monocytes.

Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10

Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naive or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naive and pre-activated T cells in which IL-10 and IDO play important roles.

Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10

Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naive or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naive and pre-activated T cells in which IL-10 and IDO play important roles.