title: Clostridium difficile-induced colitis in mice is independent of leukotrienes.
abstract: Clostridium difficile is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis in healthcare settings. However, the host factors involved in the intestinal inflammatory response and pathogenesis of C. difficile infection (CDI) are largely unknown. Here we investigated the role of leukotrienes (LTs), a group of pro-inflammatory lipid mediators, in CDI. Notably, the neutrophil chemoattractant LTB4, but not cysteinyl (cys) LTs, was induced in the intestine of C57BL/6 mice infected with either C. difficile strain VPI 10463 or strain 630. Genetic or pharmacological ablation of LT production did not ameliorate C. difficile colitis or clinical signs of disease in infected mice. Histological analysis demonstrated that intestinal neutrophilic inflammation, edema and tissue damage in mice during acute and severe CDI were not modulated in the absence of LTs. In addition, CDI induced a burst of cytokines in the intestine of infected mice in a LT-independent manner. Serum levels of anti-toxin A immunoglobulin (Ig) G levels were also not modulated by endogenous LTs. Collectively, our results do not support a role for LTs in modulating host susceptibility to CDI in mice.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA; CAPES Foundation, Ministry of Education of Brazil, Brasília, DF 70040-020, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Trindade
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, The University of Michigan, 1500 East Medical Center Drive, 3119 Taubman Center, Ann Arbor, MI 48109, USA.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Theriot
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan, 1150 West Medical Center Drive, 5641 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Jhansi L
authors.initials: JL
authors.lastname: Leslie
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan, 1150 West Medical Center Drive, 5641 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Carlson
authors.affiliation: Unit for Laboratory Animal Medicine, The University of Michigan, 1301 Catherine Street, 4107 Medical Science Building I, Ann Arbor, MI 48109, USA.
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Bergin
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, The University of Michigan, 1500 East Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, The University of Michigan, 1500 East Medical Center Drive, 3119 Taubman Center, Ann Arbor, MI 48109, USA; Department of Microbiology and Immunology, The University of Michigan, 1150 West Medical Center Drive, 5641 Medical Science II, Ann Arbor, MI 48109, USA.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232, USA. Electronic address: d.aronoff@vanderbilt.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
mesh_terms: D000818:Animals; D016360:Clostridioides difficile / Q000254:growth & development* / Q000276:immunology; D003015:Clostridium Infections / Q000382:microbiology* / Q000473:pathology*; D003092:Colitis / Q000382:microbiology* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D015289:Leukotrienes / Q000378:metabolism*; D008810:Mice, Inbred C57BL
chemical_list: D015289:Leukotrienes
keywords: Clostridium difficile; Eicosanoid; Leukotriene; Nosocomial infection