Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation

Miki Yamamoto-Hino, Masatoshi Muraoka, Shu Kondo, Ryu Ueda, Hideyuki Okano, Satoshi Goto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The innate immune system is the first line of defense encountered by invading pathogens. Delayed and/or inadequate innate immune responses can result in failure to combat pathogens, whereas excessive and/or inappropriate responses cause runaway inflammation. Therefore, immune responses are tightly regulated from initiation to resolution and are repressed during the steady state. It is well known that glycans presented on pathogens play important roles in pathogen recognition and the interactions between host molecules and microbes; however, the function of glycans of host organisms in innate immune responses is less well known. Here, we show that innate immune quiescence and strength of the immune response are controlled by host glycosylation involving a novel UDP-galactose transporter called Senju. In senju mutants, reduced expression of galactose-containing glycans resulted in hyperactivation of the Toll signaling pathway in the absence of immune challenges. Genetic epistasis and biochemical analyses revealed that Senju regulates the Toll signaling pathway at a step that converts Toll ligand Spatzle to its active form. Interestingly, Toll activation in immune-challenged wild type (WT) flies reduced the expression of galactose-containing glycans. Suppression of the degalactosylation by senju overexpression resulted in reduced induction of Toll-dependent expression of an antimicrobial peptide, Drosomycin, and increased susceptibility to infection with Gram-positive bacteria. These data suggest that Senju-mediated galactosylation suppresses undesirable Toll signaling activation during the steady state; however, Toll activation in response to infection leads to degalactosylation, which raises the immune response to an adequate level and contributes to the prompt elimination of pathogens.

Original languageEnglish
Pages (from-to)5809-5814
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number18
DOIs
Publication statusPublished - 2015 May 5

Keywords

  • Galactose
  • Glycosylation
  • Innate immunity
  • Nucleotide sugar transporter
  • Toll pathway

ASJC Scopus subject areas

  • General

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