In line with the fi ndings that CD14 contributes to LPSinduced lung infl ammation in mice, a number of studies have shown that CD14 is essential for the host defense response in the lung against Gram-negative bacteria, such as nontypeable Haemophilus infl uenzae, a possible cause of community acquired pneumonia, and A. baumannii and E. coli, which are frequent inducers of nosocomial pneumonia (Table 1) . Nontypeable H. infl uenzae expresses the TLR4 ligands LPS and lipooligosaccharide on its cell wall, as well as several TLR2 ligands, including lipoproteins and porins. Previously, we found that activa tion of alveolar macrophages by nontypeable H. infl uenzae depended on expression of TLR4, TLR2, and CD14 [30] . Moreover, bacterial clearance after intranasal infection with nontypeable H. infl uenzae was markedly reduced in CD14-defi cient and TLR4-defi cient mice, as well as in TLR2-defi cient mice at later stages of the disease [30] . Interestingly, despite impaired bacterial clearance in CD14-defi cient and TLR4-defi cient mice, the infl ammatory response in the lung was strongly reduced in TLR4 defi cient mice, but elevated in CD14 defi cient mice. Similar observations were made with encapsulated H. infl uenzae in TLR4-mutant mice [31] . Furthermore, clearance of nontypeable H. infl uenzae was also significantly impaired in MyD88-defi cient mice, but not in mice lacking functional TRIF [30] . In a similar manner, CD14 was involved in the host defense response against A. baumanii [25] . CD14-defi cient mice, like TLR4defi cient mice, suff ered from impaired bacterial clearance in the lungs and enhanced bacterial dissemination after intranasal infection with A. baumannii. However, unlike TLR4-defi cient mice, CD14-defi cient mice developed similar infl ammatory responses compared to wild-type mice. Th ese fi ndings suggest a role for CD14 in antibacterial responses against nontypeable H. infl uenzae and A. baumannii. Although the role of TLR4 (and TLR2) in phagocytic killing is controversial, it is unknown whether CD14 is involved in such processes. Th e role of CD14 in E. coli-induced pneumonia was determined in anti-CD14 antibody treated rabbits. Intravenous anti-CD14 antibody treatment of rabbits inoculated with E. coli by bronchial instillation, resulted in decreased bacterial clearance from the lungs, but had no eff ect on neutrophil infi ltration or cytokine release in the lungs [32] . However, anti-CD14 treatment protected against sustained hypotension and reduced the levels of nitrate and nitrite in the blood. Th e contribution of CD14 to E. coli-induced pneumonia has not been investigated in mice, whereas the role of the other components of the LPS receptor complex (TLR4, MD-2, MyD88, TRIF) has been determined using gene-defi cient or mutant mice. Although analysis of bacterial clearance after intranasal infection of TLR4-mutant mice with E. coli produced inconsistent results [33] , lack of MD-2 or TRIF resulted in impaired bacterial clearance after E. coli instillation in the lungs [34, 35] . Moreover, E. coli-induced neutrophil accumulation and cytokine release was signifi cantly reduced in mice devoid of functional TLR4, MD-2, MyD88 or TRIF [33] [34] [35] . Th ese fi ndings indicate that signaling through the TLR4 receptor complex is essential in the host defense response against E. coli, and suggests that CD14 may contribute to these E. coli-induced responses.