Pneumolysin, a Protein Toxin of Streptococcus pneumoniae, Induces Nitric Oxide Production from Macrophages
JS Braun, R Novak, G Gao, PJ Murray… - Infection and …, 1999 - Am Soc Microbiol
JS Braun, R Novak, G Gao, PJ Murray, JL Shenep
Infection and immunity, 1999•Am Soc MicrobiolNitric oxide (NO) production by inducible NO synthase (iNOS) during inflammation is an
essential element of antimicrobial immunity but can also contribute to host-induced tissue
damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing
hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-
positive organisms, the bacterial factors contributing to host NO production are poorly
characterized. We show that a soluble toxin of Streptococcus pneumoniae, pneumolysin …
essential element of antimicrobial immunity but can also contribute to host-induced tissue
damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing
hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-
positive organisms, the bacterial factors contributing to host NO production are poorly
characterized. We show that a soluble toxin of Streptococcus pneumoniae, pneumolysin …
Abstract
Nitric oxide (NO) production by inducible NO synthase (iNOS) during inflammation is an essential element of antimicrobial immunity but can also contribute to host-induced tissue damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-positive organisms, the bacterial factors contributing to host NO production are poorly characterized. We show that a soluble toxin of Streptococcus pneumoniae, pneumolysin (Pln), is a key component initiating NO production from macrophages. In contrast to wild-type bacteria, a mutant of S. pneumoniae lacking Pln failed to elicit NO production from murine macrophages. Purified recombinant Pln induced NO production at low concentrations and independently of exogenous gamma interferon (IFN-γ) priming of RAW 264.7 macrophages. However, IFN-γ was essential for Pln-induced NO production, since primary macrophages from mice lacking the IFN-γ receptor or interferon regulatory factor 1, a transcription factor essential for iNOS expression, failed to produce NO when stimulated with Pln. In addition, Pln acts as an agonist of tumor necrosis factor alpha and interleukin 6 production in macrophages. The properties of Pln, previously identified as a pore-forming hemolysin, also include a role as a general inflammatory agonist.
American Society for Microbiology