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Malaria-associated L-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal Salmonella bacteremia. | LitMetric

AI Article Synopsis

  • Coinfection with malaria and nontyphoidal Salmonella can lead to severe bloodstream infections, as malaria appears to weaken the intestinal barrier in humans.
  • Research in mice showed that malaria infection causes a deficiency in L-arginine, which is linked to increased histamine levels and intestinal permeability, leading to harmful bacterial translocation.
  • Supplementing mice with L-arginine or L-citrulline improved gut health by reducing inflammation and strengthening the intestinal barrier, suggesting that dietary interventions may help lower malaria-related deaths in humans.

Article Abstract

Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop L-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of L-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with L-arginine or L-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with L-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing L-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811760PMC
http://dx.doi.org/10.1128/IAI.00380-13DOI Listing

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