Single immunoglobulin interleukin-1 receptor-related molecule impairs host defense during pneumonia and sepsis caused by streptococcus pneumoniae

Dana C. Blok, Miriam H P Van Lieshout, Arie J. Hoogendijk, Sandrine Florquin, Onno J. De Boer, Cecilia Garlanda, Alberto Mantovani, Cornelis Van'T Veer, Alex F. De Vos, Tom Van Der Poll

Research output: Contribution to journalArticlepeer-review

Abstract

Streptococcus pneumoniae is a common cause of pneumonia and sepsis. Toll-like receptors (TLRs) play a pivotal role in the host defense against infection. In this study, we sought to determine the role of single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR a.k.a. TIR8), a negative regulator of TLR signaling, in pneumococcal pneumonia and sepsis. Wild-type and SIGIRR-deficient (sigirr-/-) mice were infected intranasally (to induce pneumonia) or intravenously (to induce primary sepsis) with S. pneumoniae and euthanized after 6, 24, or 48 h for analyses. Additionally, survival studies were performed. sigirr-/-mice showed delayed mortality during lethal pneumococcal pneumonia. Accordingly, sigirr-/-mice displayed lower bacterial loads in lungs and less dissemination of the infection 24 h after the induction of pneumonia. SIGIRR deficiency was associated with increased interstitial and perivascular inflammation in lung tissue early after infection, with no impact on neutrophil recruitment or cytokine production. sigirr-/-mice also demonstrated reduced bacterial burdens at multiple body sites during S. pneumoniae sepsis. sigirr-/-alveolar macrophages and neutrophils exhibited an increased capacity to phagocytose viable pneumococci. These results suggest that SIGIRR impairs the antibacterial host defense during pneumonia and sepsis caused by S. pneumoniae.

Original languageEnglish
Pages (from-to)542-552
Number of pages11
JournalJournal of Innate Immunity
Volume6
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

  • Gram-positive bacterial infections
  • Innate immunity
  • Pneumococcal pneumonia
  • Sepsis
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)

Fingerprint Dive into the research topics of 'Single immunoglobulin interleukin-1 receptor-related molecule impairs host defense during pneumonia and sepsis caused by streptococcus pneumoniae'. Together they form a unique fingerprint.

Cite this