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.