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.
