Vibrio cholerae O1 Ogawa detoxified lipopolysaccharide structures as inducers of cytokines and oxidative species in macrophages.
Multidrug resistance in several strains of Vibrio cholerae has encouraged anti-cholera vaccine developmental attempts using various subcellular moieties. In order to examine the immunological efficacy of detoxified LPS (dLPS)-derived saccharide immunogens, ex vivo activation of mouse peritoneal macrophages (MPhis) was investigated. The immunomodulatory effect was evaluated via induction of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin (IL)-1 alpha and IL-6 and acceleration of nitric oxide (NO) and reactive oxygen species (ROS). Immunologically active structures triggered mouse peritoneal MPhis to secrete cytokines and release NO/ROS, even at concentrations as low as 12.5 microg ml(-1). It was found that the O-specific polysaccharide moiety was more immunologically efficient than the glycolipid one, probably due to the position of 3-deoxy-D-manno-octulosonic acid. The results revealed effective structure-immunomodulating relationships of dLPS-derived moieties that are desirable in subcellular anti-cholera vaccine design.
Paulovičová
Ema
E
Slovak Academy of Sciences, Institute of Chemistry, Centre for Glycomics, Centre of Excellence GLYCOMED, Department of Immunochemistry of Glycoconjugates, Bratislava, Slovakia.
Kováčová
Elena
E
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Bystrický
Slavomír
S
Slovak Academy of Sciences, Institute of Chemistry, Centre for Glycomics, Centre of Excellence GLYCOMED, Department of Immunochemistry of Glycoconjugates, Bratislava, Slovakia.
D000818:Animals; D001428:Bacterial Vaccines; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019081:O Antigens / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014734:Vibrio cholerae / Q000378:metabolism*
D001428:Bacterial Vaccines; D016207:Cytokines; D019081:O Antigens; D017382:Reactive Oxygen Species; D009569:Nitric Oxide