title: Immune response to diphtheria toxin-mediated depletion complicates the use of the CD11c-DTR(tg) model for studies of bacterial gastrointestinal infections.
abstract: Dendritic cells play an important role in the immune response against pathogens, as they are responsible for the activation and control of both innate and adaptive immune responses. The CD11c-DTR(tg) model, which allows transient elimination of dendritic cells by diphtheria toxin-treatment (DTx), has been extensively used to study the importance of this immune cell during steady-state and infection conditions in mice. Infecting dendritic cell-depleted mice orally with Yersinia pseudotuberculosis results in a markedly reduced level of infection compared with infection of non-depleted mice. We show here that it is not the lack of dendritic cells per se that is responsible for the reduced infection efficiency, instead it is an immune response induced by the DTx-treatment that prevents the bacteria from establishing colonization in Peyer's patches. The DTx-induced depletion initiates an immune response, with elevated serum levels of keratinocyte-derived cytokine (KC) and recruitment of polymorphonuclear neutrophils to dendritic cell-containing organs, such as Peyer's patches. Since the window for having an animal depleted of dendritic cells is limited in time for this model, the DTx-mediated effect on the immune system complicates the use of this model in studies of early events during bacterial infections.
authors: Department of Molecular Biology, Umeå Centre for Microbial Research, Laboratory for Molecular Infection Medicine Sweden, Umeå University, 901 87 Umeå, Sweden.
authors: Linda
authors: L
authors: Westermark
authors: Anna
authors: A
authors: Fahlgren
authors: Maria
authors: M
authors: Fällman
mesh_terms: D000818:Animals; D018845:CD11 Antigens / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004167:Diphtheria Toxin / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007107:Immune System; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D018845:CD11 Antigens; D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins