Defects in the IL12IFNy Pathway

IL-12 is secreted by dendritic cells and macrophages, and IL-12R signaling induces the synthesis of IFN-y by helper T cells, cytotoxic T cells, and NK cells (see Chapter 4). Mutations in the genes encoding IL-12p40, the IL-12RP1 chain, and both chains of the IFN-y receptor, as well as some hypomorphic mutations in STAT1, all result in susceptibility to environmental Mycobacterium species (often called atypical mycobacteria), such as Mycobacterium avium, Mycobacterium kansasii, and Mycobacterium for-tuitum. IKKy/NEMO mutations also lead to susceptibility to intracellular pathogens including mycobacteria, as discussed in the previous section.

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