In 2000, Arbour and colleagues reported that two polymorphisms of the TLR4 gene were present in a higher proportion of individuals who are hyporesponsive to inhaled LPS (149) . This finding led to a number of studies investigating the potential impact of these TLR4 polymorphisms on the course of infectious diseases and the development of septic shock and TLR4 polymorphisms (150) (151) (152) . These polymorphisms do not seem to confer sus-ceptibility to all Gram-negative infections, because other groups (153, 154) have shown no correlation in other infectious diseases such as meningococcal disease, and again one should be mindful that very significant hypofunctioning TLR4 alleles are likely to have a very strong negative selection pressure across the generations (155) . TLR-2 polymorphisms have also been linked to susceptibility to staphylococcal infection (156) and lepromatous leprosy (157, 158) . Although some of these studies are still relatively small in scale, they reinforce the important role of TLRs in pathogen recognition and immune response in humans. CD14 polymorphisms, key accessory molecules for TLR signaling, have been associated with increased prevalence of positive bacterial culture findings and sepsis attributed to Gramnegative infections in a critically ill population (159) , as well as the susceptibility to chronic Chlamydia pneumoniae infection in patients with coronary artery disease (160) .