In contrast to the essential role of pulmonary TLR4 and CD14 in the host defense response against most Gramnegative bacteria, we found that TLR4 was not involved and CD14 played a remarkable detrimental role in the host response to B. pseudomallei, the causative organism of melioidosis (the most common cause of communityacquired sepsis in Southeast Asia) [39, 40] . CD14defi cient mice infected intranasally with B. pseudomallei were protected from mortality, accompanied by enhanced bacterial clearance in the lung, blood and liver, and reduced cellular infi ltration in the lung [39] , whereas the course of disease in TLR4-defi cient mice was indistinguishable from wild-type mice [40] . Moreover, intranasal administration of sCD14 to CD14-defi cient mice partially reversed the phenotype into that of wild-type mice [40] . Interestingly, these fi ndings in B. pseudo mallei-infected CD14-defi cient mice strongly resemble our previous results found with TLR2-defi cient mice, and are in line with the observation that B. pseudomallei expresses an atypical LPS which signals through TLR2 [39] . Whether CD14 interacts with TLR2 in B. pseudo mallei-induced responses, and by which mechanism these receptors facilitate the growth and dissemination of B. pseudomallei after intranasal infection remains to be determined.