Of mice and men: innate immunity in pneumococcal pneumonia

Abstract

Pneumococcal pneumonia is characterised by an intense inflammatory response induced mainly by cell wall components of the bacterium. Recognition of cell wall components by Toll-like receptors (TLRs) induces intracellular signalling pathways that culminate in the activation of pro-inflammatory genes through nuclear factor κB (NF-κB). Tumour necrosis factor-alpha (TNFα) is one of the earliest mediators produced and induces a second wave of pro- and anti-inflammatory cytokines that orchestrate the immune response. The magnitude of this response in patients with pneumococcal pneumonia is a complex network and many factors must be considered in the analysis of the cytokine production pattern. First, bacterial growth and the inflammatory response are dynamic processes, produced initially as a local phenomenon with a late systemic extension. Second, host characteristics, such as different cytokine gene polymorphisms, can cause a distinct immune response. Finally, other microorganism determinants and even the immunomodulatory effect of antimicrobials may play a role in cytokine production. Recent data on innate immunity against Streptococcus pneumoniae gathered from the murine model of pneumonia, from studies of human genetic polymorphisms associated with increased susceptibility to pneumococcal infection, and from human clinical trials are discussed. Special emphasis has been placed on the description of the chronology of the complex network of innate immunity triggered by pneumococcal infection.