Protective role of mincle in bacterial pneumonia by regulation of neutrophil mediated phagocytosis and extracellular trap formation

Atul Sharma, Anthony L. Steichen, Christopher N. Jondle, Bibhuti B. Mishra, Jyotika Sharma

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Background. Nosocomial infections with Klebsiella pneumoniae are a frequent cause of Gram-negative bacterial sepsis. To understand the functioning of host innate immune components in this disorder, we examined a previously uninvestigated role of the C-type lectin receptor Mincle in pneumonic sepsis caused by K. pneumoniae.Methods. Disease progression in wild-type and Mincle-/- mice undergoing pulmonary infection with K. pneumoniae was compared. Results. Whereas the wild-type mice infected with a sublethal dose of bacteria could resolve the infection with bacterial clearance and regulated host response, the Mincle-/- mice were highly susceptible with a progressive increase in bacterial burden, despite their ability to mount an inflammatory response that turned to an exaggerated hyperinflammation with the onset of severe pneumonia. This correlated with severe lung pathology with a massive accumulation of neutrophils in their lungs. Importantly, Mincle -/- neutrophils displayed a defective ability to phagocytize nonopsonic bacteria and an impaired ability to form extracellular traps (NETs), an important neutrophil function against invading pathogens, including K. pneumoniae.Conclusion. Our results demonstrate protective role of Mincle in host defense against K. pneumoniae pneumonia by coordinating bacterial clearance mechanisms of neutrophils. A novel role for Mincle in the regulation of neutrophil NET formation may have implications in chronic disease conditions characterized by deregulated NET formation.

Original languageEnglish (US)
Pages (from-to)1837-1846
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number11
DOIs
StatePublished - Jun 1 2014
Externally publishedYes

Keywords

  • Clec4e
  • Klebsiella
  • Mincle
  • NETs
  • neutrophils
  • phagocytosis
  • pneumonia
  • sepsis

ASJC Scopus subject areas

  • General Medicine

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