Bacterial meningitis strikes around 1,000 people in the U.S. every year, according to the CDC, and 10-14% of those cases are fatal. Researchers are drilling down into what happens in the spinal fluid to make a bad case of meningitis and deadly one, but they still know little about the role of one protein involved in the process: a component of the immune system called complement C3. This week, mBio features a study that shows the presence of complement C3 in spinal fluid correlates with survival, a fact that indicates it plays a key role in the pathogenesis of bacterial meningitis.
Looking for proteins that indicate survival, the team used samples of cerebrospinal fluid (CSF) from 80 patients with bacterial meningitis and 10 non-infected controls. The fluid samples were a useful resource for the team: they represented 40 meningitis patients who survived and 40 who did not. They measured the levels of several central nervous system and serum proteins that had been identified as possible indicators in earlier proteomics work. Goonetilleke et al. found that complement C3 was present at significantly higher concentration in the spinal fluid of patients who later pulled through than in patients who later died.
What does this mean? Complement C3 aids innate immunity by coating pathogens with fragments of itself, which stimulates destruction of the pathogen by other components of the immune system or the release of proinflammatory mediators. It's easy to see that if a person's spinal fluid is depleted in C3, this cascade of immune reactions wouldn't be effective and the pathogen might run rampant, endangering the patient's life. Knowing that C3 is present at greater concentrations in patients who survive, it may well serve as a prognostic marker - a sort of oracle that can indicate just how severe a case of bacterial meningitis is bound to become.
Another interesting aspect of the study is what it says about apoptosis, a process that has been the target of experimental therapies for bacterial meningitis. In mice, apoptosis (programmed cell death) is an important mechanism for neuronal cell death, which can cause neurological problems in survivors. If apoptosis were also a factor in human neuronal damage from bacterial meningitis, then treatments that inhibit apoptosis could prevent some of the neurological damage wrought by the pathogen. But in their study, Goonetilleke et al. found that standard apoptosis markers were absent in patients' spinal fluid, suggesting that apoptosis is not a factor in human cases of meningitis and that treatment with citicoline and caspase inhibitors to prevent apoptosis is unlikely to have an effect.