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Medzhitov, R., Schneider, D. S., & Soares, M. P. (2012). Disease Tolerance as a Defense Strategy. Science, 335(6071), 936–941. Added by: Dr. Enrique Feoli (07/05/2022, 16:23) Last edited by: Dr. Enrique Feoli (04/08/2025, 21:18) |
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| Resource type: Journal Article DOI: 10.1126/science.1214935 BibTeX citation key: Medzhitov2012 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Disease Tolerance Creators: Medzhitov, Schneider, Soares Collection: Science |
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| Abstract |
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The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen’s presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of “disease tolerance” into the conceptual tool kit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases.
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| Notes |
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The avoidance strategy works through alteration of host behavior and requires that the host detect the risk of pathogen exposure before being infected. Sensing pathogens before infection is mediated primarily through the olfactory and gustatory systems, although visual cues can also be used in some species. Pathogen presence in the environment is detected through various molecular proxies of high pathogen density, such as volatile metabolites specifically produced by microorganisms, including pathogens. For example, cadaverine, putrescine, and skatole (3-methylindole) are chemicals produced by bacterial metabolism of amino acids that occurs during putrefaction of animal tissues. Methane thiol is produced by bacterial breakdown of L-methionine and contributes to the characteristic body odor associated with high bacterial densities on the skin. At high doses, these chemicals have foul odor (as perceived by humans) and thus report on high bacterial densities and therefore high risk of infection. Their detection by the olfactory system triggers aversive behavior (at least in some species) that helps to reduce the risk of infection (7). For example, a subset of formyl-peptide receptors is expressed in the mammalian vomeronasal organ, where they function as olfactory receptors and presumably detect pathogens or infected conspecifics (8, 9). The gustatory sensory system is also involved in triggering aversive behaviors and reflexes. Interestingly, the chemosensory system used to sense bitter taste also appears to be used to detect acylhomoserine lactone, a bacterial quorum-sensing molecule that signals high bacterial density (10). It is unclear to what extent different aversive behaviors are innate or learned; this likely depends on the stimulus and the host species. The mechanism of aversive behavior is best understood in Caenorhabditis elegans, where avoidance of pathogens is a learned behavior, mediated by the olfactory neurons (11, 12). Social insects also have well-documented avoidance behaviors that help minimize colony exposure to pathogens (13). Bullfrog tadpoles use chemical cues to detect and avoid infected conspecifics (14). In rodents, detection of infected conspecifics through the olfactory system controls mate selection and avoidance of social contact (7). Aversive behavior and feelings of disgust also play an important role in humans, helping to reduce pathogen exposure (15). Although pathogen avoidance can have a clear adaptive value, extreme forms of aversive behavior can be a considerable handicap, as exemplified by germophobia, a common type of obsessive-compulsive disorder.
Publisher: American Association for the Advancement of Science
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |