ABSTRACT
Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.
Subject(s)
Disease Models, Animal , Exosomes , Mesenchymal Stem Cells , Muromegalovirus , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Signal Transduction , Animals , Exosomes/metabolism , Mesenchymal Stem Cells/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-kappa B/metabolism , Muromegalovirus/physiology , Mice, Inbred C57BL , Macrophages/immunology , Cytomegalovirus Infections/therapy , Cytomegalovirus Infections/virology , Lung/virology , Lung/pathology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Herpesviridae Infections/therapy , Herpesviridae Infections/virology , Herpesviridae Infections/immunology , Pneumonia/therapy , Pneumonia/virologyABSTRACT
The recent discovery of superconductivity in infinite-layer nickelates generates tremendous research endeavors, but the ground state of their parent compounds is still under debate. Here, we report experimental evidence for the dominant role of Kondo scattering in the underdoped Nd1-xSrxNiO2 thin films. A resistivity minimum associated with logarithmic temperature dependence in both longitudinal and Hall resistivities are observed in the underdoped Nd1-xSrxNiO2 samples before the superconducting transition. At lower temperatures down to 0.04 K, the resistivities become saturated, following the prediction of the Kondo model. A linear scaling behavior [Formula: see text] between anomalous Hall conductivity [Formula: see text] and conductivity [Formula: see text]is revealed, verifying the dominant Kondo scattering at low temperature. The effect of weak (anti-)localization is found to be secondary. Our experiments can help in clarifying the basic physics in the underdoped Nd1-xSrxNiO2 infinite-layer thin films.
