Intractable mycobacterial infections associated with genetic defects in the receptor for interferon gamma: what does this tell us about immunity to mycobacteria?

The attenuated strain of Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used vaccine in the world. In most children, inoculation of live BCG vaccine is harmless although it occasionally leads to a benign regional adenitis. In rare cases, however, vaccination causes disseminated BCG infection, which may be lethal. Impaired immunity of the host is generally thought to be the pathogenic mechanism. Disseminated BCG infection has been reported in children with inherited immune disorders. Most of these children had severe combined immunodeficiency, which is characterized by an absence of T cells, and some had chronic granulomatous disease, which is marked by an impairment of the phagocyte respiratory burst. Rare cases of BCG infection have also been reported in association with the acquired immunodeficiency syndrome. We examined the five genes coding for interferon-c, interferon-cR1, IRF1, TNF-a, and TNF-aR1 in a child with fatal idiopathic disseminated BCG infection. We found a mutation of the gene for interferon-cR1. There was no detectable interferon-cR1 on the cells from the affected child. These findings provide further evidence of the importance of interferonc in the response to mycobacterial infection. (N Engl J Med 1996;335:1956–61)