The protective effect of immunoglobulin in murine tuberculosis is dependent on IgG glycosylation
Por:
Olivares N., Marquina B., Mata-Espinoza D., Zatarain-Barron Z.L., Pinzón C.E., Estrada I., Parada C., Collin M., Rook G., Hernandez-Pando R.
Publicada:
1 dic 2013
Resumen:
Antibodies have demonstrated having a protective effect in animal models of tuberculosis (TB). These experiments have considered the specificity of antigen recognition and the different isotypes and subclasses as significant contributors of this effect. However, the carbohydrate chain heterogeneity on the Fc region of IgG (Fc-IgG) can play an important role in modulating the immune response. Patients with TB usually have high titers of specific IgG; however, the carbohydrate associated with Fc-IgG usually lacks galactose. To assess the effect of this abnormal IgG in murine pulmonary TB, we evaluated the specificity of recognition to Mycobacterium tuberculosis antigens in vitro and protective effects in vivo comparing human intravenous immunoglobulin (IVIg) and IVIg treated with an endoglycosidase to remove the glycan residues (EndoS-treated IVIg). Our results showed similar antigen recognition. The study of distribution and kinetics of IVIg in serum and bronchial lavage after intraperitoneal (i.p.) administration in mice showed that IVIg circulates for 21 days. Finally, the protective effect of intact and EndoS-treated IVIg administered by i.p was studied in a murine model of progressive TB. IVIg treatment caused reduction in pulmonary bacilli loads, larger granulomas, and less pneumonia, while animals treated with EndoS-treated IVIg were not protected compared with control animals. Thus, IVIg has a protective activity in experimental pulmonary TB, and this effect requires intact Fc oligosaccharides. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
Filiaciones:
Olivares N.:
Univ Nacl Autonoma Mexico, Inst Biomed Res, Mexico City 04510, DF, Mexico
Marquina B.:
National Institute of Medical Sciences and Nutrition Salvador Zubirán, DelegaciónTlalpan, Mexico
Mata-Espinoza D.:
National Institute of Medical Sciences and Nutrition Salvador Zubirán, DelegaciónTlalpan, Mexico
Zatarain-Barron Z.L.:
National Institute of Medical Sciences and Nutrition Salvador Zubirán, DelegaciónTlalpan, Mexico
Pinzón C.E.:
Univ Nacl Autonoma Mexico, Inst Biomed Res, Mexico City 04510, DF, Mexico
Estrada I.:
National School of Biological Sciences, IPN, Mexico D.F, Mexico
Parada C.:
Univ Nacl Autonoma Mexico, Inst Biomed Res, Mexico City 04510, DF, Mexico
Collin M.:
Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden
Rook G.:
Centre for Clinical Microbiology, UCL (University College London), London, United Kingdom
Hernandez-Pando R.:
National Institute of Medical Sciences and Nutrition Salvador Zubirán, DelegaciónTlalpan, Mexico
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