Human Placental MSC-Secreted IL-1β Enhances Neutrophil Bactericidal Functions during Hypervirulent Klebsiella Infection

Li Tzu Wang, Hsiu Huan Wang, Hui Chun Chiang, Li Yueh Huang, Sheng Kang Chiu, L. Kristopher Siu, Ko Jiunn Liu, Men Luh Yen, B. Linju Yen

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Article number108188
JournalCell Reports
Volume32
Issue number13
DOIs
Publication statusPublished - Sept 29 2020
Externally publishedYes

Keywords

  • bone marrow
  • human mesenchymal stem cells
  • hypervirulent
  • interleukin-1β
  • Klebsiella pneumoniae
  • placenta
  • polymorphonuclear neutrophil

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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