title: Mast cells and histamine alter intestinal permeability during malaria parasite infection.
abstract: Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: rapotts@ucdavis.edu.
authors.forename: Rashaun A
authors.initials: RA
authors.lastname: Potts
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: cmtiffany@ucdavis.edu.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Tiffany
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: npakpour@ucdavis.edu.
authors.forename: Nazzy
authors.initials: N
authors.lastname: Pakpour
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: kllokken@ucdavis.edu.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Lokken
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: crtiffany@ucdavis.edu.
authors.forename: Connor R
authors.initials: CR
authors.lastname: Tiffany
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: kcheung@ucdavis.edu.
authors.forename: Kong
authors.initials: K
authors.lastname: Cheung
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: rmtsolis@ucdavis.edu.
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: sluckhart@ucdavis.edu.
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
mesh_terms: D000818:Animals; D060085:Coinfection; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000097:blood / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008415:Mastocytosis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000469:parasitology*; D010539:Permeability; D012480:Salmonella Infections / Q000276:immunology / Q000378:metabolism
chemical_list: D006633:Histamine Antagonists; D006632:Histamine
keywords: Bacteremia; Co-infection; Histamine; Malaria; Mast cell; Plasmodium; Salmonella