title: The insulin receptor substrate Chico regulates antibacterial immune function in Drosophila.
abstract: BACKGROUND
  Molecular and genetic studies in model organisms have recently revealed a dynamic interplay between immunity and ageing mechanisms. In the fruit fly Drosophila melanogaster, inhibition of the insulin/insulin-like growth factor signaling pathway prolongs lifespan, and mutations in the insulin receptor substrate Chico extend the survival of mutant flies against certain bacterial pathogens. Here we investigated the immune phenotypes, immune signaling activation and immune function of chico mutant adult flies against the virulent insect pathogen Photorhabdus luminescens as well as to non-pathogenic Escherichia coli bacteria.
  
  
  RESULTS
  We found that D. melanogaster chico loss-of-function mutant flies were equally able to survive infection by P. luminescens or E. coli compared to their background controls, but they contained fewer numbers of bacterial cells at most time-points after the infection. Analysis of immune signaling pathway activation in flies infected with the pathogenic or the non-pathogenic bacteria showed reduced transcript levels of antimicrobial peptide genes in the chico mutants than in controls. Evaluation of immune function in infected flies revealed increased phenoloxidase activity and melanization response to P. luminescens and E. coli together with reduced phagocytosis of bacteria in the chico mutants. Changes in the antibacterial immune function in the chico mutants was not due to altered metabolic activity.
  
  
  CONCLUSIONS
  Our results indicate a novel role for chico in the regulation of the antibacterial immune function in D. melanogaster. Similar studies will further contribute to a better understanding of the interconnection between ageing and immunity and lead to the identification and characterization of the molecular host components that modulate both important biological processes.
authors.affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, 800 Science and Engineering Hall, 22nd Street NW, Washington, D.C., 20052 USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: McCormack
authors.affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, 800 Science and Engineering Hall, 22nd Street NW, Washington, D.C., 20052 USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, 800 Science and Engineering Hall, 22nd Street NW, Washington, D.C., 20052 USA.
authors.forename: Upasana
authors.initials: U
authors.lastname: Shokal
authors.affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, 800 Science and Engineering Hall, 22nd Street NW, Washington, D.C., 20052 USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Kenney
authors.affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, 800 Science and Engineering Hall, 22nd Street NW, Washington, D.C., 20052 USA.
authors.forename: Dustin
authors.initials: D
authors.lastname: Cooper
authors.affiliation: Insect Infection and Immunity Laboratory, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, 800 Science and Engineering Hall, 22nd Street NW, Washington, D.C., 20052 USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Eleftherianos
keywords: Ageing; Chico; Drosophila melanogaster; Infection; Innate immunity; Insect pathogen; Long-lived mutant; Photorhabdus