The vaccine Mycobacterium bovis BCG is administrated to prevent early age tuberculosis in endemic areas. BCG is a live vaccine with a low incidence of complications. However, local or disseminated BCG infection may occur, in particular in immunodeficient individuals. Chronic granulomatous disease (CGD), a deficiency in the superoxide-producing phagocyte NADPH oxidase, is a primary immune deficiency and one of the most frequent congenital defects of phagocyte in humans.
The study analyses the role of the phagocyte NADPH oxidase NOX2 in the defense against BCG. An extensive literature review suggested that BCG infection is by far the most common mycobacterial disease in CGD patients (220 published cases). The authors therefore studied BCG infection in several CGD mouse models showing that these were highly susceptible to BCG infection with a mortality rate of ~50%.
As compared to the wild type, CGD mice showed a markedly increased release of cytokines, an altered granuloma structure, and were unable to restrain mycobacteria within granulomas. Rescue of the phagocyte NADPH oxidase in macrophages was sufficient to protect mice from BCG infection and to sequester the mycobacteria within granulomas. Thus, superoxide generation by macrophages plays an important role for the defense against BCG infection and prevents overshooting release of proinflammatory cytokines.
Study: Bacillus Calmette-Guerin Infection in NADPH Oxidase Deficiency: Defective Mycobacterial Sequestration and Granuloma Formation, Christine Deffert, Michela G. Scha¨ppi, Jean-Claude Pach, Julien Cachat, Dominique Vesin, Ruth Bisig, Xiaojuan Ma Mulone, Tiina Kelkka, Rikard Holmdahl, Irene Garcia, Maria L. Olleros, Karl-Heinz Krause, PLoS Pathog, doi:10.1371/journal.ppat.1004325, published 4 September 2014.