Bacterial Infections and Pneumonia: What is the Role of Toll-Like Receptors?

Bacterial pneumonia is an important disease and the most frequent cause of death due to an infection worldwide. Host defense against inhaled pathogens is essential in preventing microbes from gaining access to the lower respiratory tract where they might cause tissue damage. The innate immune system provides the first line of defense and hence is involved in the recognition of invading pathogens. In order to detect microbial motifs, innate immune cells express a panel of so-called pattern recognition receptors. The most important recognition receptors are Toll-like receptors (TLRs) of which 10 have been identified in humans. Each TLR can identify a specific set of microbial motifs, which then leads to the activation of innate immune cells and the release of proinflammatory mediators. The distinct role of selected TLRs during bacterial pneumonia has been extensively studied in animal models. While host defense against Streptococcus pneumoniae depends on the simultaneous involvement of TLR2, TLR4 and TLR9, the immune response during most Gram-negative pneumonias requires the presence of TLR4. Although these data disclosed important information they also revealed a high redundancy in the requirements for TLRs in vivo. Genetic association studies in humans in turn confirmed the redundancy since only deficiencies in common downstream signaling molecules were found associated with increased susceptibility to bacterial pneumonia. Immunotherapeutic possibilities that could target TLRs directly are therefore limited, and currently confined to TLRs’ role as adjuvants and activators of adaptive immune responses in vaccine development.

Keywords: TLRs, bacterial pneumonia, Streptococcus pneumonia, Gram-negative pneumonias.