Surfactant Protein D Binds Selectively toKlebsiella pneumoniaeLipopolysaccharides Containing Mannose-Rich O-Antigens

Abstract

Surfactant protein D (SP-D) plays important roles in the regulation of innate immune responses in the lung. We have previously shown that SP-D can agglutinate and enhance the macrophage-dependent killing of specific unencapsulated phase variants of Klebsiella pneumoniae. In the present studies, we used 16 clinical isolates of Klebsiella representing four O-serotypes and examined the interaction of SP-D with their isolated LPSs. Although SP-D bound to the core oligosaccharide of rough LPS from all isolates, it selectively bound to smooth forms of LPS expressed by O-serotypes with mannose-rich repeating units in their O-polysaccharides. SP-D was more potent in agglutinating unencapsulated phase variants of O-serotypes expressing these SP-D “reactive” O-polysaccharides, and more effectively inhibited the adhesion of these serotypes to lung epithelial cells. This novel anti-adhesion activity required the multimerization of trimeric SP-D subunits (dodecamers). Klebsiella serotypes expressing “nonreactive” LPS O-Ags were isolated at a significantly higher frequency from patients with K. pneumoniae. Our findings suggest that SP-D plays important roles in the clearance of opportunistic Gram-negative bacteria and contributes to known serotypic differences in the pathogenicity of Klebsiella through specific interactions with O-polysaccharides.

Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling

“…3,4 For example, SP-D prevents dissemination of infectious microbes by their biological activities including agglutination and growth inhibition. [5][6][7] SP-D also promotes clearance of microbes by enhancing phagocytosis in macrophages. 8,9 In addition, SP-D interacts with the other pattern-recognition molecules including Toll-like receptors (TLRs) and TLR-associated molecules CD14 and MD-2, and regulates inflammatory responses.…”

Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

“…The epithelial attachment of the bacteria was inhibited by SP-D in a dose-dependent manner in vitro (79). However, the minimal concentration of SP-D needed to inhibit the adhesion of the noncapsulated variants of Klebsiella to the epithelial cells was four times lower for the O3 serotype, which expresses the polymannose epitope, than that required for the O1 serotype, which lacks this epitope.…”

“…Because capsules can interfere with the expression or function of adhesins required for the colonization of epithelial cells by the organisms, it is likely that most of the bacteria colonizing the upper respiratory tract or other epithelial surfaces are in the noncapsulated phase (19,57,81,83). Lung collectin SP-D, which reacts with a conserved region of the LPS core, may provide early protection against all strains of noncapsulated phenotypes either by opsonizing the bacteria to enhance their phagocytosis or by agglutinating the bacteria, which may inhibit their adhesion to the upper respiratory epithelium (71,79). However, as discussed above, productive binding of SP-D to the LPS core region is influenced by the molecular structure of the O antigen.…”

Crystal Structure of Trimeric Carbohydrate Recognition and Neck Domains of Surfactant Protein A

“…SP-A binds specifically to dipalmitoylphosphatidylcholine, the most abundant phospholipid species in surfactant (26), whereas SP-D binds to the minor surfactant component phosphatidylinositol (27,28). Both bind to the lipopolysaccharide moieties that decorate bacterial surfaces; SP-A recognizes the lipid A component of lipopolysaccharide (29,30), whereas SP-D binds to the core oligosaccharide and O-oligosaccharides (31). Electron micrographs and other data indicate that the globular CRD and collagen-like domains in both surfactant proteins are oriented proximal and distal, respectively, to the membrane surface (32,33).…”