TIGR4 strain causes more severe disease than WU2 strain in a mouse model of Streptococcus pneumoniae meningitis: a common pathogenic role for interferon-γ

Streptococcus pneumoniae (S. pneumoniae) meningitis causes debilitating neurological symptoms and acute fatalities in patients, and long-term neurological sequelae in some survivors. Current vaccines do not protect against all 94 known S. pneumoniae capsular serotypes, many of which are capable of causing pneumococcal meningitis (PM). We here compare the pathogenic outcomes of two clinically virulent isolates of S. pneumoniae, serotype 3 strain WU2 and serotype 4 strain TIGR4, in a murine model of PM. At an identical infectious dosage of 103 CFU administered via the intracerebroventricular route, significantly greater mortality, interleukin (IL)1β and IL6 production, and blood-brain barrier dysfunction occurred in TIGR4-induced PM compared to PM caused by WU2. Higher bacterial counts in the cerebrospinal fluid and nitrite/nitrate in serum were observed 40 h post inoculation with TIGR4 compared to mice infected with WU2. Similar to our previous findings in WU2 PM, interferon-γ was an essential driver of the pathogenesis of TIGR4 PM, suggesting that this cytokine may be a common pathogenic agent across a range of pneumococcal meningitides and, thus, a potential therapeutic target for intervention.