T he innate immune proteins surfactant protein D (SP-D) and SP-A are pattern recognition receptors (PRRs) that belong to the superfamily of collagen-containing C-type lectins known as the collectins, which in humans also includes CL-L1, CL-P1, and mannan-binding lectin (1). Collectins can enhance proinflammatory molecules such as cytokines, and reactive oxygen species in phagocytes, by interacting with cell surface receptors or by the scavenging of bacterial molecules (2). As first-line host defense molecules in the lung, SP-D and SP-A target pathogens for neutralization and rapid clearance through interaction with surface carbohydrate structures and promotion of phagocytosis by alveolar macrophages. Bacterial surface lipopolysaccharide (LPS) is a target ligand for immune system defense molecules, and recognition by SP-D of the LPS of various Gram-negative bacterial species, including Escherichia coli (3), Haemophilus influenzae (4, 5), Salmonella enterica serovar Minnesota (3), Bordetella species (6), and Pseudomonas aeruginosa (5), has been previously reported. Many of those studies suggested that lung collectins bind to the LPS core and strongly implicated heptose (Hep) and glucose residues in this binding.H. influenzae is a common cause of human disease worldwide. Serotype b capsular strains cause invasive bacteremic infections such as meningitis and septicemia (7,8), while the more prevalent nonencapsulated or nontypeable H. influenzae strains are a common cause of otitis media (9), sinusitis, conjunctivitis, and acute lower respiratory tract infections. Surface-expressed LPS is involved in each stage of the pathogenesis of infections-colonization of the upper respiratory tract, systemic dissemination, and cytotoxic injury to target tissues (10). Host molecules that recognize the LPS of these organisms are important in limiting pathogenicity. In the newborn and in young infants, innate immune components play a key role in frontline defense against infection, while premature infants have reduced collectin levels and are more susceptible to infection (11).The lipid A region of the LPS of H. influenzae bacteria is linked to a triheptosyl inner core by a single phosphorylated 3-deoxy-Dmanno-oct-2-ulosonic acid (Kdo) moiety. While the LPS glycoform structures and the genetic blueprint for biosynthesis are known for many H. influenzae strains, the oligosaccharides of the exposed LPS outer core provide substantial heterogeneity within and between strains (12, 13), hindering detailed investigation of the interaction with the pulmonary collectins. The structure of the wild-type (WT) H. influenzae strain RM153 (Eagan) LPS (
