Role of MiR-466 in Mesenchymal Stromal Cell Derived Extracellular Vesicles Treating Inoculation Pneumonia Caused by Multidrug-resistant Pseudomonas Aeruginosa

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2021 Jan 19

PMID 33463070

Citations 16

Authors

Meng-Meng Shi

Ying-Gang Zhu

Jia-Yang Yan

Jean-Jacques Rouby

Hanssa Summah

Antoine Monsel

Jie-Ming Qu

Affiliations

Soon will be listed here.

Abstract

Rationale: The effects of mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) on multidrug-resistant pseudomonas aeruginosa (MDR-PA)-induced pneumonia remain unclear.

Materials And Methods: MicroRNA array and RT-PCR were used to select the major microRNA in MSC EVs. Human peripheral blood monocytes were obtained and isolated from qualified patients. The crosstalk between MSCs/MSC EVs and macrophages in vitro was studied. MDR-PA pneumonia models were further established in C57BL/6 mice and MSC EVs or miR-466 overexpressing MSC EVs were intratracheally instilled.

Results: MiR-466 was highly expressed in MSC EVs. MSCs and miR-466 promoted macrophage polarization toward Type 2 phenotype through TIRAP-MyD88-NFκB axis. Moreover, cocultured macrophages with miR-466 overexpressing MSCs significantly increased the phagocytosis of macrophages. MSC EVs significantly reduced mortality and decreased influx of BALF neutrophils, proinflammatory factor levels, protein, and bacterial load in murine MDR-PA pneumonia. Administration of miR-466 overexpressing MSC EVs further alleviated the inflammatory severity.

Conclusions: MSC-derived EVs containing high levels of miR-466 may partly participate in host immune responses to MDR-PA. Both MSCs and MSC EVs have therapeutic effects in treating MDR-PA-induced pneumonia.

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References

Locati M, Mantovani A, Sica A . Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol. 2013; 120:163-84. DOI: 10.1016/B978-0-12-417028-5.00006-5. View

Matute-Bello G, Downey G, Moore B, Groshong S, Matthay M, Slutsky A . An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011; 44(5):725-38. PMC: 7328339. DOI: 10.1165/rcmb.2009-0210ST. View

Raes G, Van den Bergh R, De Baetselier P, Hassanzadeh Ghassabeh G, Scotton C, Locati M . Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells. J Immunol. 2005; 174(11):6561. DOI: 10.4049/jimmunol.174.11.6561. View

Park J, Kim S, Lim H, Liu A, Hu S, Lee J . Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe pneumonia. Thorax. 2018; 74(1):43-50. PMC: 6295323. DOI: 10.1136/thoraxjnl-2018-211576. View

Mao Y, Xu J, Seeley E, Tang X, Xu L, Zhu Y . Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Pulmonary Infection Caused by Pseudomonas aeruginosa via Inhibiting Overproduction of Prostaglandin E2. Stem Cells. 2015; 33(7):2331-42. DOI: 10.1002/stem.1996. View

Shi M, Zhu Y, Yan J, Rouby J, Summah H, Monsel A . Role of miR-466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug-resistant Pseudomonas aeruginosa. Clin Transl Med. 2021; 11(1):e287. PMC: 7805403. DOI: 10.1002/ctm2.287. View

Monsel A, Zhu Y, Gennai S, Hao Q, Hu S, Rouby J . Therapeutic Effects of Human Mesenchymal Stem Cell-derived Microvesicles in Severe Pneumonia in Mice. Am J Respir Crit Care Med. 2015; 192(3):324-36. PMC: 4584251. DOI: 10.1164/rccm.201410-1765OC. View

Torres A, Niederman M, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H . International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the.... Eur Respir J. 2017; 50(3). DOI: 10.1183/13993003.00582-2017. View

Morrison T, Jackson M, Cunningham E, Kissenpfennig A, McAuley D, OKane C . Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer. Am J Respir Crit Care Med. 2017; 196(10):1275-1286. PMC: 5694830. DOI: 10.1164/rccm.201701-0170OC. View

10.

Xiao M, Wang Y, Yang Q, Fan X, Brown M, Kong F . Antimicrobial susceptibility of Pseudomonas aeruginosa in China: a review of two multicentre surveillance programmes, and application of revised CLSI susceptibility breakpoints. Int J Antimicrob Agents. 2012; 40(5):445-9. DOI: 10.1016/j.ijantimicag.2012.07.002. View

11.

Kalil A, Metersky M, Klompas M, Muscedere J, Sweeney D, Palmer L . Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016; 63(5):e61-e111. PMC: 4981759. DOI: 10.1093/cid/ciw353. View

12.

Rittirsch D, Hoesel L, Ward P . The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol. 2006; 81(1):137-43. DOI: 10.1189/jlb.0806542. View

13.

Ma F, Liu X, Li D, Wang P, Li N, Lu L . MicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. J Immunol. 2010; 184(11):6053-9. DOI: 10.4049/jimmunol.0902308. View

14.

Mizgerd J, Skerrett S . Animal models of human pneumonia. Am J Physiol Lung Cell Mol Physiol. 2007; 294(3):L387-98. DOI: 10.1152/ajplung.00330.2007. View

15.

Gilmore T . Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006; 25(51):6680-4. DOI: 10.1038/sj.onc.1209954. View

16.

Krasnodembskaya A, Samarani G, Song Y, Zhuo H, Su X, Lee J . Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol. 2012; 302(10):L1003-13. PMC: 3362255. DOI: 10.1152/ajplung.00180.2011. View

17.

Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F . Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008; 319(5867):1244-7. DOI: 10.1126/science.1153124. View

18.

Curley G, Jerkic M, Dixon S, Hogan G, Masterson C, OToole D . Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli-Induced Acute Respiratory Distress Syndrome. Crit Care Med. 2016; 45(2):e202-e212. DOI: 10.1097/CCM.0000000000002073. View

19.

Mukherjee B, Paul J, Mukherjee S, Mukhopadhyay R, Das S, Naskar K . Antimony-Resistant Leishmania donovani Exploits miR-466i To Deactivate Host MyD88 for Regulating IL-10/IL-12 Levels during Early Hours of Infection. J Immunol. 2015; 195(6):2731-42. DOI: 10.4049/jimmunol.1402585. View

20.

Ionescu L, Byrne R, van Haaften T, Vadivel A, Alphonse R, Rey-Parra G . Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. 2012; 303(11):L967-77. PMC: 3532523. DOI: 10.1152/ajplung.00144.2011. View