Myeloid-derived suppressor cells exacerbate poly(I:C)-induced lung inflammation in mice with renal injury and older
Zhiqi Xie1,2, Haoyang Zhou2, Masanori Obana3,4,5,6
1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China.
Abstract:
Viral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that myeloid-derived suppressor cells (MDSCs) are abundant in these patient groups; however, their roles in the progression of viral pneumonia remain unclear. In this study, we observed a substantial increase in MDSCs in a mouse model of renal ischemia/reperfusion (I/R) injury and in older mice. When intranasal polyinosinic-polycytidylic acid (poly(I:C)) administration was used to mimic viral pneumonia, mice with renal I/R injury exhibited more severe lung inflammation than sham mice challenged with poly(I:C). In addition, MDSC depletion attenuated lung inflammation in mice with I/R injury. Similar results were obtained in older mice compared with those in young mice. Furthermore, adoptive transfer of in vitro-differentiated MDSCs exacerbated poly(I:C)-induced lung inflammation. Taken together, these experimental results suggest that the increased proportion of MDSCs in mice with renal I/R injury and in older mice exacerbates poly(I:C)-induced lung inflammation. These findings have important implications for the treatment and prevention of severe lung inflammation caused by viral pneumonia.
Insights
Myeloid-derived suppressor cells (MDSCs) worsen viral pneumonia severity. Reducing MDSCs eased lung inflammation in mice with kidney injury or in older mice, suggesting new therapeutic targets.
Area of Science:
- Immunology
- Pulmonology
- Pathology
Background:
- Viral pneumonia poses a significant global health risk, particularly for the elderly and those with pre-existing conditions.
- Myeloid-derived suppressor cells (MDSCs) are elevated in vulnerable populations, but their specific role in viral pneumonia progression is not well understood.
Purpose of the Study:
- To investigate the role of myeloid-derived suppressor cells (MDSCs) in exacerbating lung inflammation during viral pneumonia.
- To determine if MDSCs contribute to increased severity in older mice or those with renal ischemia/reperfusion (I/R) injury.
Main Methods:
- Utilized a mouse model of viral pneumonia induced by intranasal polyinosinic-polycytidylic acid (poly(I:C)) administration.
- Examined MDSC levels in mice with renal I/R injury and in aged mice compared to controls.
- Assessed lung inflammation following MDSC depletion or adoptive transfer of MDSCs.
Main Results:
- Mice with renal I/R injury and older mice showed increased MDSCs and more severe lung inflammation after poly(I:C) challenge.
- Depletion of MDSCs significantly reduced lung inflammation in these mice.
- Transferring MDSCs worsened poly(I:C)-induced lung inflammation.
Conclusions:
- Elevated myeloid-derived suppressor cells (MDSCs) exacerbate viral pneumonia-induced lung inflammation, particularly in contexts of renal I/R injury and aging.
- MDSCs represent a potential therapeutic target for managing severe viral pneumonia.
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