Function of SLAM-Associated Protein (SAP) in Acute Pneumoseptic Bacterial Infection

Jitendra K. Tripathi, Atul Sharma, Kuldeep Gupta, Houda Abdelrahman, Pooja Chauhan, Bibhuti B. Mishra, Jyotika Sharma

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Sepsis resulting from acute pneumonic infections by Gram-negative bacteria is often characterized by dysfunction of innate immune components. Here we report a previously unrecognized innate protective function of SAP, an adaptor protein primarily reported in T cells, NK cells, and NKT cells, during acute pneumonic infection with Klebsiella pneumoniae (KPn). SAP-deficient mice were highly susceptible to this infection with elevated systemic bacterial spread and increased lung damage. While the overall influx of infiltrating cells in the lungs remained largely intact, increased mortality of SAP-deficient mice correlated with increased accumulation of large NK1.1 + cells harboring bacteria and an impairment of neutrophil extracellular trap formation in vivo during KPn pneumonia, which likely facilitated bacterial outgrowth. Neutrophils were found to express SAP; however, adoptive transfer experiment supported a neutrophil-extrinsic function of SAP in neutrophil extracellular trap formation. Collectively, these data present the first report depicting innate protective function of SAP in an acute pulmonary infection.

Original languageEnglish (US)
Pages (from-to)4345-4353
Number of pages9
JournalJournal of Molecular Biology
Volume431
Issue number21
DOIs
StatePublished - Oct 4 2019
Externally publishedYes

Keywords

  • NK1.1+ cells
  • SLAM-associated protein, SAP, Sh2d1a
  • neutrophil extracellular traps
  • neutrophils
  • phagocytes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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