2011
DOI: 10.1371/journal.pone.0016839
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A Two-Gene Balance Regulates Salmonella Typhimurium Tolerance in the Nematode Caenorhabditis elegans

Abstract: Lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. However, using the nematode Caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme LYS-7 renders animals susceptible to killing by the fatal fungal human pathogen Cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria Salmonella Typhimurium. This trade-off in immunological susceptibility in C. elegans is further mediat… Show more

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Cited by 29 publications
(21 citation statements)
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“…Knockdown of lys-7 also caused enhanced susceptibility toward P. aeruginosa and, interestingly, this pathogen suppresses the expression of lys-7 as part of its pathogenicity strategy 28 . In contrast, more resistance toward S. Typhimurium was observed in a lys-7 mutant, which was also shown to be more susceptible to infection with the fungus Cryptococcus neoformans 43 . Furthermore, knockdown of lys-2 , lys-5 and lys-7 led to decreased resistance against B. thuringiensis , whereas overexpression of lys-5 and lys-7 , but not lys-2 , resulted in an increase in resistance 18 .…”
Section: Lysozymesmentioning
confidence: 97%
“…Knockdown of lys-7 also caused enhanced susceptibility toward P. aeruginosa and, interestingly, this pathogen suppresses the expression of lys-7 as part of its pathogenicity strategy 28 . In contrast, more resistance toward S. Typhimurium was observed in a lys-7 mutant, which was also shown to be more susceptible to infection with the fungus Cryptococcus neoformans 43 . Furthermore, knockdown of lys-2 , lys-5 and lys-7 led to decreased resistance against B. thuringiensis , whereas overexpression of lys-5 and lys-7 , but not lys-2 , resulted in an increase in resistance 18 .…”
Section: Lysozymesmentioning
confidence: 97%
“…Although C. elegans has no cell-mediated immunity, work by a number of groups has revealed a complex innate immune approach for disease resistance comprising avoidance behaviors (58,60) and physical barriers (25). For systemic immunity, the animal is believed to depend purely upon the secretion and action of antimicrobial molecules, including lectins (43,54,66,81), lysozymes (6,17,27,43,44,50,54,67,77,81), and antibacterial factors (34,62). Both lines of defense have been shown to be regulated by a number of signaling pathways, of which the p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs), insulin signaling/DAF-2, and transforming growth factor ␤ (TGF-␤)/ DBL-1 pathways are the most significant (see reference 30 for a recent review).…”
Section: Caenorhabditis Elegans and Immunitymentioning
confidence: 99%
“…Interestingly, recent work from our laboratory identified a complex genetic trade-off in the worm immune system, such that changes that increased susceptibility to killing by C. neoformans through the loss of the immune genes lys-7 and abl-1 simultaneously enhanced tolerance to S. Typhimurium, suggesting that some aspects of C. elegans immunity may provide specialized and opposing antimicrobial activities (44).…”
Section: Cryptococcus Neoformansmentioning
confidence: 99%
“…Deletion of the protist type lysozyme LYS-7 can make C. elegans susceptible to killing by fungus Cryptococcus neoformans , a fatal human pathogen, but enhance its tolerance to the enteric bacteria Salmonella Typhimurium . These compound responses indicate higher levels of complexity in the C. elegans innate immune system [42]. C. elegans can respond to pathogens by generating reactive oxygen species (ROS) in the intestine while synchronically instigating an oxidative stress response which is dependent on transcriptional regulator DAF-16 to protect adjacent tissues [43].…”
Section: Interactions Between Microbial Pathogens and C Elegansmentioning
confidence: 99%