https://scholars.lib.ntu.edu.tw/handle/123456789/546013
Title: | Human Placental MSC-Secreted IL-1β Enhances Neutrophil Bactericidal Functions during Hypervirulent Klebsiella Infection | Authors: | Wang, Li-Tzu Wang, Hsiu-Huan Chiang, Hui-Chun Huang, Li-Yueh Chiu, Sheng-Kang Siu, L Kristopher Liu, Ko-Jiunn MEN-LUH YEN Yen, B Linju |
Keywords: | Klebsiella pneumoniae; bone marrow; human mesenchymal stem cells; hypervirulent; interleukin-1β; placenta; polymorphonuclear neutrophil | Issue Date: | 29-Sep-2020 | Publisher: | CELL PRESS | Journal Volume: | 32 | Journal Issue: | 13 | Source: | Cell reports | Abstract: | Hypervirulent Klebsiella pneumoniae (hvKP) causes severe infections even in healthy individuals by escaping surveillance and killing from polymorphonuclear neutrophils (PMNs), the first-line leukocytes in bacterial infections; moreover, the emergence of multidrug-resistant strains further limits treatment options. We therefore assess whether multilineage mesenchymal stem cells (MSCs), best known for immunomodulation toward T cells, could be therapeutic for highly virulent bacterial infections via modulation of PMNs. We find that both bone marrow MSCs and placental MSCs (PMSCs) preserve in vitro PMN survival, but only PMSCs significantly enhance multiple PMN bactericidal functions, including phagocytosis, through secretion of interleukin-1β (IL-1β). PMSC treatment of hvKP-infected mice suppresses T and natural killer (NK) cell responses as expected but can preferentially recruit PMNs and enhance antibacterial functions to allow for disease survival; IL-1β knockdown in PMSCs significantly decreases hvKP clearance, worsening survival and resulting in 100% lethality. Our data strongly implicate the possible use of PMSCs for infections of PMN-resistant hvKP strains. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/546013 | ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2020.108188 | SDG/Keyword: | interleukin 1beta; IL1B protein, human; interleukin 1beta; abdominal infection; animal experiment; animal model; animal tissue; apoptosis; Article; bacterial clearance; bactericidal activity; bone marrow derived mesenchymal stem cell; cell survival; cell viability; controlled study; cytokine release; extracellular trap; female; gene knockdown; human; human cell; immunomodulation; in vitro study; in vivo study; Klebsiella infection; Klebsiella pneumoniae; lethality; lymphocyte function; male; mesenchymal stem cell; mesenchymal stem cell transplantation; mouse; natural killer cell; neutrophil; nonhuman; peritoneal cavity; phagocytosis; placental mesenchymal stem cell; priority journal; protein function; T lymphocyte; therapy effect; genetics; Klebsiella infection; mesenchymal stem cell; metabolism; neutrophil; placenta; pregnancy; Female; Humans; Interleukin-1beta; Klebsiella Infections; Mesenchymal Stem Cells; Neutrophils; Placenta; Pregnancy |
Appears in Collections: | 醫學系 |
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