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The protective effect of immunoglobulin in murine tuberculosis is dependent on IgG glycosylation

Olivares, Nesty ; Marquina, Brenda ; Mata-Espinoza, Dulce ; Zatarain-Barron, Zyanya L. ; Espitia Pinzon, Clara ; Estrada, Iris ; Parada, Cristina ; Collin, Mattias LU orcid ; Rook, Graham and Hernandez-Pando, Rogelio (2013) In Pathogens and Disease 69(3). p.176-183
Abstract
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... (More)
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 21days. 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. This work compares conventional fully glycosylated and deglycosylated IVIg determining their mycobacterial antigen recognition by two dimensional Western-blotting, specific mycobacterial antigen recognition by ELISA, kinetics of distribution after intraperitoneal administration, and protective efficiency by evaluating pulmonary bacilli loads and tissue damage after i.p. administration during early infection in a model of progressive pulmonary tuberculosis. The results add to the growing body of information that antibodies have a protective effect at least in animal models of tuberculosis. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
tuberculosis, antibodies, glycosylation, experimental models, IVIG, Immunotherapy
in
Pathogens and Disease
volume
69
issue
3
pages
176 - 183
publisher
Wiley-Blackwell
external identifiers
  • wos:000327216600002
  • scopus:84896781254
ISSN
2049-632X
DOI
10.1111/2049-632X.12069
language
English
LU publication?
yes
id
b394ae8e-925e-493b-bb0d-4483abcdfdcb (old id 4196613)
date added to LUP
2016-04-01 09:48:15
date last changed
2022-04-27 07:39:23
@article{b394ae8e-925e-493b-bb0d-4483abcdfdcb,
  abstract     = {{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 21days. 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. This work compares conventional fully glycosylated and deglycosylated IVIg determining their mycobacterial antigen recognition by two dimensional Western-blotting, specific mycobacterial antigen recognition by ELISA, kinetics of distribution after intraperitoneal administration, and protective efficiency by evaluating pulmonary bacilli loads and tissue damage after i.p. administration during early infection in a model of progressive pulmonary tuberculosis. The results add to the growing body of information that antibodies have a protective effect at least in animal models of tuberculosis.}},
  author       = {{Olivares, Nesty and Marquina, Brenda and Mata-Espinoza, Dulce and Zatarain-Barron, Zyanya L. and Espitia Pinzon, Clara and Estrada, Iris and Parada, Cristina and Collin, Mattias and Rook, Graham and Hernandez-Pando, Rogelio}},
  issn         = {{2049-632X}},
  keywords     = {{tuberculosis; antibodies; glycosylation; experimental models; IVIG; Immunotherapy}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{176--183}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Pathogens and Disease}},
  title        = {{The protective effect of immunoglobulin in murine tuberculosis is dependent on IgG glycosylation}},
  url          = {{http://dx.doi.org/10.1111/2049-632X.12069}},
  doi          = {{10.1111/2049-632X.12069}},
  volume       = {{69}},
  year         = {{2013}},
}