Malaria-associated l-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal salmonella bacteremia

Jennifer Y. Chau, Caitlin M. Tiffany, Shilpa Nimishakavi, Jessica A. Lawrence, Nazzy Pakpour, Jason P. Mooney, Kristen L. Lokken, George H. Caughey, Renee M Tsolis, Shirley Luckhart

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 Larginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans.

Original languageEnglish (US)
Pages (from-to)3515-3526
Number of pages12
JournalInfection and Immunity
Volume81
Issue number10
DOIs
StatePublished - 2013

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Bacteremia
Mast Cells
Salmonella
Malaria
Arginine
Mastocytosis
Coinfection
Citrulline
Permeability
Parasites
Pathology
Bacterial Translocation
Adherens Junctions
Salmonella enterica
Tight Junctions
Dietary Supplements
Ileum
Interleukin-4
Histamine
Biological Availability

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Malaria-associated l-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal salmonella bacteremia. / Chau, Jennifer Y.; Tiffany, Caitlin M.; Nimishakavi, Shilpa; Lawrence, Jessica A.; Pakpour, Nazzy; Mooney, Jason P.; Lokken, Kristen L.; Caughey, George H.; Tsolis, Renee M; Luckhart, Shirley.

In: Infection and Immunity, Vol. 81, No. 10, 2013, p. 3515-3526.

Research output: Contribution to journalArticle

Chau, JY, Tiffany, CM, Nimishakavi, S, Lawrence, JA, Pakpour, N, Mooney, JP, Lokken, KL, Caughey, GH, Tsolis, RM & Luckhart, S 2013, 'Malaria-associated l-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal salmonella bacteremia', Infection and Immunity, vol. 81, no. 10, pp. 3515-3526. https://doi.org/10.1128/IAI.00380-13
Chau, Jennifer Y. ; Tiffany, Caitlin M. ; Nimishakavi, Shilpa ; Lawrence, Jessica A. ; Pakpour, Nazzy ; Mooney, Jason P. ; Lokken, Kristen L. ; Caughey, George H. ; Tsolis, Renee M ; Luckhart, Shirley. / Malaria-associated l-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal salmonella bacteremia. In: Infection and Immunity. 2013 ; Vol. 81, No. 10. pp. 3515-3526.
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