In the later part of the 19th century, Ilya Metchnikoff began to develop his ideas on phagocytosis (derived from the Greek word phagein, meaning 'to eat') as a mechanism of host defense using translucent star fish larvae and Daphnia water fleas to directly observe white corpuscle function in vivo. Some 50 years later, Baldridge and Gerard noted that this activity is accompanied by a massive oxygen consumption that is biologically distinct from mitochondrial respiration. It is now known that the 'respiratory burst' characteristic of professional phagocytic cells is accomplished by NOX2, a specialized NADPH oxidase enzyme complex. In this issue of Nature Immunology, Bustamante and colleagues describe a 'macrophage-specific' mutation in CYBB (which encodes the gp91phox component of NOX2) in two families with mycobacterial disease and suggest that this is a susceptibility gene to add to those already shown to compromise interferon-gamma-mediated immunity.
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