Diverse mechanisms employed by Toxoplasma gondii to inhibit IFN-γ-induced major histocompatibility complex class II gene expression

2006 ◽  
Vol 8 (8) ◽  
pp. 1994-2005 ◽  
Author(s):  
Christine Lang ◽  
Michaela Algner ◽  
Nicole Beinert ◽  
Uwe Groß ◽  
Carsten G.K. Lüder
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
Toxoplasma Gondii ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Ifn Γ

scholarly journals Mycobacterium bovis BCG Urease Attenuates Major Histocompatibility Complex Class II Trafficking to the Macrophage Cell Surface

2004 ◽  
Vol 72 (7) ◽  
pp. 4200-4209 ◽  
Author(s):  
Khalid Sendide ◽  
Ala-Eddine Deghmane ◽  
Jean-Marc Reyrat ◽  
Amina Talal ◽  
Zakaria Hmama
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Major Histocompatibility Complex Class ◽  
Mycobacterium Bovis ◽  
Surface Expression ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Ifn Γ

ABSTRACT We have previously shown that Mycobacterium tuberculosis attenuates cell surface expression of major histocompatibility complex class II molecules in response to gamma interferon (IFN-γ) by a mechanism dependent on intracellular sequestration of α,β dimers. In this study we examined whether intracellular alkalinization due to mycobacterial urease could account for the defect in intracellular trafficking of class II molecules. Phagocytosis of wild-type Mycobacterium bovis BCG was associated with secretion of ammonia intracellularly, which increased substantially upon addition of exogenous urea to the culture medium. Increased intracellular ammonia, due to urea degradation by the bacterium, correlated with inhibition of class II surface expression. Conversely, no ammonia was detected in cells infected with a urease-negative mutant strain of M. bovis BCG, which also displayed a reduced effect on surface expression of class II molecules. A direct cause-effect relationship between urease and class II molecule trafficking was established with experiments where cells ingesting beads coated with purified urease showed an increased ammonia level and decreased surface expression of class II in response to IFN-γ. In contrast to BCG, infection of macrophages with Mycobacterium smegmatis, which expresses relatively greater urease activity in cell-free culture, had a marginal effect on both the intracellular level of ammonia and class II expression. The limited effect of M. smegmatis was consistent with a failure to resist intracellular killing, suggesting that urease alone is not sufficient to resist macrophage microbicidal mechanisms and that this is required for a more distal effect on cell regulation. Our results demonstrate that alkalinization of critical intracellular organelles by pathogenic mycobacteria expressing urease contributes significantly to the intracellular retention of class II dimers.

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