title: Activation of innate immune responses by Haemophilus influenzae lipooligosaccharide.
abstract: A Gram-negative pathogen Haemophilus influenzae has a truncated endotoxin known as lipooligosaccharide (LOS). Recent studies on H. influenzae LOS highlighted its structural and compositional implications for bacterial virulence; however, the role of LOS in the activation of innate and adaptive immunity is poorly understood. THP-1 monocytes were stimulated with either lipopolysaccharide (LPS) from Escherichia coli or LOS compounds derived from H. influenzae Eagan, Rd, and Rd lic1 lpsA strains. Cell surface expression of key antigen-presenting, costimulatory, and adhesion molecules, as well as gene expression of some cytokines and pattern recognition receptors, were studied. Eagan and Rd LOS had a lower capacity to induce the expression of ICAM-1, CD40, CD58, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) compared to LPS. In contrast, antigen-presenting (HLA-ABC or HLA-DR) and costimulatory (CD86) molecules and NOD2 were similarly upregulated in response to LOS and LPS. LOS from a mutant Rd strain (Rd lic1 lpsA) consistently induced higher expression of innate immune molecules than the wild-type LOS, suggesting the importance of phosphorylcholine and/or oligosaccharide extension in cellular responses to LOS. An LOS compound with a strong ability to upregulate antigen-presenting and costimulatory molecules combined with a low proinflammatory activity may be considered a vaccine candidate to immunize against H. influenzae.
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Joshua
authors.initials: J
authors.lastname: Choi
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cox
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: William
authors.initials: W
authors.lastname: McCready
authors.forename: Marina
authors.initials: M
authors.lastname: Ulanova
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D004926:Escherichia coli / Q000276:immunology; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000032:analysis; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006680:HLA Antigens; D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D011971:Receptors, Immunologic; C023023:lipid-linked oligosaccharides; D018799:Intercellular Adhesion Molecule-1