In addition to the membrane-bound TLRs, which sense pathogens outside cells or in endosomes, the innate immune system has evolved to equip cells with pattern recognition receptors that detect infection or cell damage in the cytoplasm (see Fig. 4-1 and Table 4-3). The two major classes of these cytoplasmic receptors are NOD-like receptors and RIG-like receptors. These cytoplasmic receptors, like TLRs, are linked to signal transduction pathways that promote inflammation or type I interferon production. The ability of the innate immune system to detect infection in the cytoplasm is important because parts of the normal life cycles of some microbes, such as viral gene translation and viral particle assembly, take place in the cytoplasm. Some bacteria and parasites have mechanisms to escape from phagocytic vesicles into the cytoplasm. Microbes can produce toxins that create pores in host cell plasma membranes, including endosomal membranes, through which microbial molecules can enter the cytoplasm. These pores can also result in changes in the concentration of endogenous molecules in the cytoplasm, which are reliable signs of infection and damage and are detected by the cytoplasmic receptors.
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