Adoptive transfer of interleukin-4 programmed macrophages reduces lung inflammation during betacoronavirus infection.

Murine interleukin-4-educated macrophages (M(IL4)) exert well-established anti-inflammatory effects. Here, we sought to determine whether bone marrow-derived M(IL4) could attenuate lung inflammation and serve as a cell-based therapeutic strategy for viral infectious diseases. Mice were intranasally infected with murine hepatitis virus (MHV)-A59. M(IL4)s generated in vitro were intravenously transferred into mice infected with MHV-A59 in two doses administered on days 3 and 4 post-infection. The distribution of transferred cells was examined by flow cytometry. Lung histopathology, chemokines (CXCL-1, CCL3, and CCL2), cytokines (IL-1β, TNF, and IFN-γ), viral titers, blood cell counts, and macrophage subsets were evaluated. Transferred M(IL4)s localized to the lung and bronchoalveolar lavage fluid (BALF), and the cells retained their anti-inflammatory capacity. Systemic delivery of M(IL4) attenuated MHV-A59-induced inflammatory responses, as evidenced by reduced pro-inflammatory cytokine levels, decreased lung tissue damage, and enhanced viral clearance. Moreover, M(IL4) therapy reduced the abundance of inflammatory macrophages and expression of MHC class II and CD80 markers while favoring the expansion of anti-inflammatory subsets in both BALF and lung tissue of MHV-A59-infected mice. These data provide important insights into the therapeutic potential of macrophage-based cell therapy in virus-induced lung inflammation and pave the way for further investigation of macrophages as therapy for individuals with severe cases of respiratory viral infections.