Polymorphisms that affect host susceptibility may be found at various sites in the genes encoding host receptors targeted by pathogens and may result in loss or gain of receptor-associated functions. Some SNPs may lead to multiple and diverse downstream effects, e.g. altered transcriptional response and manifestation of disease (Sakuntabhai et al., 2005) . Extracellular domain polymorphisms may have a more direct effect via altered binding of pathogen ligands to their receptors. SNPs of the innate immune system especially those affecting pathogen associated pattern recognition receptors and cytokines have been studied extensively. Changes such as Asp299Gly and Thr399Ile in the extracellular domains of LPS-binding Toll-like receptor 4 (TLR4) have been implicated in increased risk to bacterial infections (Schroder and Schumann, 2005) . These SNPs have also been associated with severe respiratory syncytial virus (RSV) bronchiolitis in infants. In this case, altered interaction of the viral fusion (F) protein, implicated as a ligand for TLR4, is regarded as the primary mechanism (Tal et al., 2004; Schroder and Schumann, 2005) . However, these TLR4 SNPs could not be correlated with meningococcal disease (Read et al., 2001) . In contrast, rare SNPs were found more commonly in the TLR4 genes of patients with meningococcal disease (Smirnova et al., 2003) . This supports the notion that rare rather than common variants of TLR4 may be associated with infectious disease susceptibility.