Adoptive transfer of interleukin-4 programmed macrophages reduces lung inflammation during betacoronavirus infection
Franciel Batista Felix1, Vinicius Amorim Beltrami2, Ana Paula Soares da Cruz Maravilha2
1Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil; Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió 57072-900, Brazil.
Abstract:
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.
Insights
Interleukin-4-educated macrophages (M(IL4)) therapy reduced lung inflammation and improved viral clearance in mice infected with a respiratory virus. This macrophage cell therapy shows promise for treating severe viral lung infections.
Area of Science:
- Immunology
- Cell Therapy
- Virology
Background:
- Murine interleukin-4-educated macrophages (M(IL4)) possess known anti-inflammatory properties.
- Viral infectious diseases, particularly respiratory infections, pose significant health challenges.
Purpose of the Study:
- To investigate the potential of bone marrow-derived M(IL4) as a cell-based therapy for lung inflammation induced by viral infection.
- To evaluate the efficacy of M(IL4) in attenuating murine hepatitis virus (MHV)-A59-induced lung inflammation and enhancing viral clearance.
Main Methods:
- Mice were infected with MHV-A59 and intravenously received M(IL4) on days 3 and 4 post-infection.
- Evaluated cell distribution, lung histopathology, inflammatory markers (chemokines, cytokines), viral titers, blood counts, and macrophage subsets via flow cytometry.
Main Results:
- Transferred M(IL4) localized to the lungs and retained anti-inflammatory capacity.
- M(IL4) therapy reduced pro-inflammatory cytokines, lung damage, and viral load, while enhancing viral clearance.
- Therapy modulated macrophage populations, decreasing inflammatory subsets and increasing anti-inflammatory ones.
Conclusions:
- Systemic M(IL4) administration effectively attenuated viral-induced lung inflammation in mice.
- Macrophage-based cell therapy holds therapeutic potential for severe respiratory viral infections.
