Pathogens

A long-standing question in immunity is how the host detects pathogens. Since many microbes are also beneficial for the host, accurate discrimination between non-pathogens and pathogens is important. Traditionally, the microbe-associated molecular patterns (MAMPs) are thought to induce the innate immune response via the Toll-like receptor signaling. Since many patho-genic as well as nonpathogenic microbes share the same MAMPs, this model is insufficient to explain why immunity is initiated only against pathogenic bacteria and not against the others. An alternative model is the so-called damage-associated molecular pattern (DAMP) hypothesis. 3,4 In this model, the host immune cells detects the DAMP signals such as the uric acid or high-mobility group box 1 (HMGB1) released by infected cells and triggers innate immune response via the Toll-like receptor sig-naling. 5-8 However, whether this is a bonafide response to the pathogen or the pathological response of the host is not yet clear. Another celebrated theory on how host detects pathogens is effector triggered immunity (ETI). First described in plants, the ETI theory suggests that the host detects virulence effector proteins from the pathogens directly or via effects on the host cellular homeostasis and responds to it by inducing beneficial innate immune responses. While host " resistance " proteins that directly detect microbial effectors are found in plants, there is no evidence for such proteins in animals in the literature. In animals, recent studies provide evidence that the bacterial effectors are recognized indirectly because of their effects on cellular homeostasis. and mammalian cell culture 18-20 have found that the host cells detects and responds to deficits in key cellular processes induced by the microbial effectors rather than detecting the microbes themselves. According to these studies, the pathogen-derived virulence factors or effectors or toxins induce decrement in the essential cellular processes such as protein translation or mitochondrial respiration or actomyosin cytoskeleton. 15 The host surveillance pathways detects these changes in essential cellular processes and responds to it by mounting an innate immune response as well as xenobiotic detoxification responses. 15 Since changes in these essential cellular processes are most likely to be caused by microbial virulence factors or toxins in the host's evolutionary history, an innate immune response to such an insult is a well-calculated response. In this special focus, the authors review recent developments in the effector triggered immunity field. Rajamuthiah and Mylonakis 21 review the recent studies, which provide evidence that the bacterial effectors …