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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
hMSCs treatment attenuates murine herpesvirus-68 (MHV-68) pneumonia through altering innate immune response via
Aiping Qin1, Xiao-Juan Wang1, Jijun Fu1
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
Abstract:
Immunocompromised individuals are particularly vulnerable to viral infections and reactivation, especially endogenous herpes viruses such as Epstein-Barr virus (EBV), a member of oncogenic gamma-herpesviruses, which are commonly linked to pneumonia and consequently significant morbidity and mortality. In the study of human and animal oncogenic gammaherpesviruses, the murine gamma-herpesviruses-68 (MHV-68) model has been applied, as it can induce pneumonia in immunocompromised mice. Mesenchymal stem cell (MSC) treatment has demonstrated therapeutic potential for pneumonia, as well as other forms of acute lung injury, in preclinical models. In this study, we aim to investigate the therapeutic efficacy and underlying mechanisms of human bone marrow-derived MSC (hMSC) on MHV-68-induced pneumonia. We found that intravenous administration of hMSCs significantly reduced lung damages, diminished inflammatory mediators and somehow inhibited MHV-68 replication. Furthermore, hMSCs treatment can regulate innate immune response and induce macrophage polarization from M1 to M2 phenotype, could significantly alter leukocyte infiltration and reduce pulmonary fibrosis. Our findings with co-culture system indicated that hMSCs effectively reduced the secretion of of inflammation-related factors and induced a shift in macrophage polarization, consistent with in vivo results. Further investigations revealed that hMSCs treatment suppressed the activation of macrophage ROS/NLRP3 signaling pathway in vivo and in vitro. Moreover, administration of MCC950, a selective NLRP3 inhibitor has been shown to effectively reduce ROS production and subsequently alleviate inflammation induced by MHV-68. Taken together, our work has shown that hMSCs can effectively protect mice from lethal MHV-68 pneumonia, which may throw new light on strategy for combating human EBV-associated pneumonia.
Insights
Human mesenchymal stem cells (hMSCs) treat MHV-68 pneumonia by reducing lung damage and inflammation. This therapy regulates immune responses and inhibits viral replication, offering potential for Epstein-Barr virus-associated pneumonia.
Area of Science:
- Immunology
- Virology
- Regenerative Medicine
Background:
- Immunocompromised individuals face risks from herpes viruses like Epstein-Barr virus (EBV), often leading to severe pneumonia.
- Murine gammaherpesvirus-68 (MHV-68) models pneumonia in mice, serving as a relevant preclinical tool.
- Mesenchymal stem cells (MSCs) show promise in treating lung injuries, including pneumonia.
Purpose of the Study:
- To investigate the therapeutic effects of human bone marrow-derived MSCs (hMSCs) on MHV-68-induced pneumonia.
- To elucidate the mechanisms by which hMSCs exert their protective effects against viral pneumonia.
Main Methods:
- Intravenous administration of hMSCs in a murine model of MHV-68 pneumonia.
- Co-culture systems to assess hMSC interactions with immune cells.
- Analysis of inflammatory mediators, viral replication, immune cell infiltration, and macrophage polarization.
- Investigation of the ROS/NLRP3 signaling pathway and the effect of NLRP3 inhibition.
Main Results:
- hMSC treatment significantly reduced lung damage, inflammatory mediators, and MHV-68 replication.
- hMSCs modulated innate immunity, promoting M2 macrophage polarization and reducing leukocyte infiltration and pulmonary fibrosis.
- Co-culture experiments confirmed hMSCs' ability to reduce inflammatory factors and induce M2 polarization.
- hMSC therapy suppressed the macrophage ROS/NLRP3 pathway; MCC950 (NLRP3 inhibitor) mimicked some protective effects.
Conclusions:
- hMSCs provide significant protection against lethal MHV-68 pneumonia in mice.
- hMSC therapy mechanism involves immune regulation, M2 macrophage polarization, and suppression of the ROS/NLRP3 pathway.
- These findings suggest hMSCs as a potential therapeutic strategy for human EBV-associated pneumonia.
