title: Intestinal FoxO signaling is required to survive oral infection in Drosophila.
abstract: The intestinal immune system is tailored to fight pathogens effectively while tolerating the indigenous microbiota. Impairments of this homeostatic interaction may contribute to the etiology of various diseases including inflammatory bowel diseases. However, the molecular architecture underlying this complex regulatory interaction is not well understood. Here, we show that the fruit fly Drosophila melanogaster has a multilayered intestinal immune system that ensures strictly localized antimicrobial responses. Enterocytes, a major cell population of the intestine, produced antimicrobial peptides (AMPs) in a FoxO- but not NF-κB-dependent manner. Consequently, animals impaired in FoxO-mediated signaling had a significantly lowered resistance to intestinal infections; they were unable to increase the expression of AMP genes and males showed an increased bacterial load in response to an infection. Conventional innate immune signaling converging onto NF-κB activation was operative in only a few regions of the intestine, comprising the proventriculus, copper cells, and intestinal stem cells. Taken together, our results imply that danger-mediated as well as conventional innate immune signaling constitute modules that contribute to the fruit fly's intestinal immune system. We propose that this special architecture ensures localized and efficient antimicrobial responses against invasive pathogens while preserving the microbiota.
authors.affiliation: Department of Zoology, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Fink
authors.affiliation: Department of Zoology, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Department of Zoology, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Knop
authors.affiliation: Department of Zoology, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Zoology, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Isermann
authors.affiliation: Department of Zoology, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.|Airway Research Center North, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: T
authors.initials: T
authors.lastname: Roeder
mesh_terms: D000284:Administration, Oral; D000818:Animals; D030801:Animals, Genetically Modified; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D058491:Bacterial Load; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000276:immunology*; D020895:Enterocytes / Q000276:immunology* / Q000382:microbiology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007422:Intestines / Q000033:anatomy & histology / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D016868:Serratia Infections / Q000276:immunology*; D012706:Serratia marcescens / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D016328:NF-kappa B