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Mannose-binding lectin and ficolin-2 do not influence humoral immune response to hepatitis B vaccine.

ABSTRACT: Host genetics appear to be an important factor in the failure to generate a protective immune response after hepatitis B (HBV) vaccination. Mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway of complement, influence the clinical outcome of HBV, and MBL deficiency has been shown to augment the humoral response to HBV vaccination in several experimental models. Here, we investigated the association of MBL and FCN2 with the humoral response to HBV vaccination in a candidate gene and functional study.A post hoc analysis of a prospective, interventional HBV vaccination study among human immunodeficiency virus type 1 (HIV-1) uninfected individuals in Kenya was conducted. Serum levels and polymorphisms of MBL and FCN2 were analysed in relation to the immune response to HBV vaccination.Protective hepatitis B surface antibody levels (? 10 mI U/mL) were evident in 251/293 (85.7%) individuals. Median MBL and FCN2 levels were similar in responders vs. non-responders with a weak trend towards lower median MBL levels in non-responders (1.0 vs. 1.6?g/mL, p=0.1). Similarly, there was no difference in four MBL and six FCN2 polymorphisms analysed in the two groups with the exception of an increased frequency of a homozygous MBL codon 57 mutation in non-responders (4 (9.5%) vs. 8 (3.2%), p=0.05) corresponding to lower MBL levels. Results were similar after adjusting for age and sex.Our study does not support a prominent role of the lectin pathway of complement in general and MBL and FCN2 in particular in the humoral immune response to HBV vaccination in African adults.

SUBMITTER: Osthoff M

PROVIDER: S-EPMC4374143 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Project description:The causative agents of Lyme borreliosis, spirochetes belonging to the Borrelia burgdorferi sensu lato group, have developed several ways to protect themselves against killing by the host complement system. In addition, it has been shown that serum sensitive isolates are (partially) protected by the Ixodes Tick Salivary Lectin Pathway Inhibitor (TSLPI) protein; a salivary gland protein that inhibits the function of Mannose Binding Lectin (MBL). MBL is a C-type lectin that recognizes oligosaccharides on pathogens and activates the complement system via the lectin pathway. MBL deficiency has been linked to a more severe course of several infectious diseases and humans with detectable antibodies against B. burgdorferi are significantly more often MBL deficient compared to humans without antibodies against B. burgdorferi. Here we set out to investigate the role of MBL in the immune response against B. burgdorferi in more detail. We demonstrate that B. burgdorferi N40 needle-infected C57BL/6 MBL deficient mice harbored significantly higher B. burgdorferi numbers in skin tissue during the early course of infection. In line with these findings they also developed higher anti-B. burgdorferi IgG serum antibodies compared to WT controls. In contrast, B. burgdorferi loads in distant tissue such as heart, joints or bladder at later time points were similar for both mouse strains. These in vivo findings were corroborated using a B. burgdorferi N40-infected I. scapularis infestation model. We showed that MBL is capable of binding B. burgdorferi through its carbohydrate recognition domains, but in vitro complement killing assays, peritoneal macrophage and whole blood stimulations, phagocytosis assays and an in vivo migration experiment did not reveal the mechanism by which MBL facilitates early clearance of B. burgdorferi. To conclude, we show a protective role of MBL in the early stages of B. burgdorferi infection, yet the underlying mechanism warrants further investigation.

Project description:Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proinflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl(+/+)) and MBL-deficient (Mbl(-/-)) mice were exposed to ozone (0.3 ppm) for up to 72 h, and bronchoalveolar lavage fluid was examined for inflammatory markers. Mean numbers of eosinophils and neutrophils and levels of the neutrophil attractants C-X-C motif chemokines 2 [Cxcl2 (major intrinsic protein 2)] and 5 [Cxcl5 (limb expression, LIX)] in the bronchoalveolar lavage fluid were significantly lower in Mbl(-/-) than Mbl(+/+) mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in transcript response profiles and networks at baseline [e.g., nuclear factor erythroid-related factor 2 (NRF2)-mediated oxidative stress response] and after exposure (e.g., humoral immune response) between Mbl(+/+) and Mbl(-/-) mice. The microarray data were further analyzed to discover several informative differential response patterns and subsequent gene sets, including the antimicrobial response and the inflammatory response. We also used the lists of gene transcripts to search the LINCS L1000CDS(2) data sets to identify agents that are predicted to perturb ozone-induced changes in gene transcripts and inflammation. These novel findings demonstrate that targeted deletion of Mbl caused differential levels of inflammation-related gene sets at baseline and after exposure to ozone and significantly reduced pulmonary inflammation, thus indicating an important innate immunomodulatory role of the gene in this model.

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Mannose-binding lectin and ficolin-2 do not influence humoral immune response to hepatitis B vaccine.

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