Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster. Proc Natl Acad Sci U S A

Global Health Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2011; 108(38):15966-71. DOI: 10.1073/pnas.1105994108
Source: PubMed


The peritrophic matrix (PM) forms a layer composed of chitin and glycoproteins that lines the insect intestinal lumen. This physical barrier plays a role analogous to that of mucous secretions of the vertebrate digestive tract and is thought to protect the midgut epithelium from abrasive food particles and microbes. Almost nothing is known about PM functions in Drosophila, and its function as an immune barrier has never been addressed by a genetic approach. Here we show that the Drosocrystallin (Dcy) protein, a putative component of the eye lens of Drosophila, contributes to adult PM formation. A loss-of-function mutation in the dcy gene results in a reduction of PM width and an increase of its permeability. Upon bacterial ingestion a higher level of expression of antibacterial peptides was observed in dcy mutants, pointing to an influence of this matrix on bacteria sensing by the Imd immune pathway. Moreover, dcy-deficient flies show an increased susceptibility to oral infections with the entomopathogenic bacteria Pseudomonas entomophila and Serratia marcescens. Dcy mutant flies also succumb faster than wild type upon ingestion of a P. entomophila toxic extract. We show that this lethality is due in part to an increased deleterious action of Monalysin, a pore-forming toxin produced by P. entomophila. Collectively, our analysis of the dcy immune phenotype indicates that the PM plays an important role in Drosophila host defense against enteric pathogens, preventing the damaging action of pore-forming toxins on intestinal cells.

Download full-text


Available from: Bruno Lemaitre, May 17, 2015
  • Source
    • "The PM of insect alimentary canal is similar to the mucous lining of vertebrate gut, separating the midgut epithelium and its food contents, being a protective lining for the epithelium. In addition, the PM plays important roles in nutrient absorption, and it is the first barrier to pathogens and toxins ingested during feeding (Terra, 2001; Terra and Ferreira, 2005; Bolognesi et al., 2008; Kuraishi et al., 2011; Levy et al., 2011; Hu et al., 2012a,b; Jariyapan et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The midgut is a region of the digestive tract of bees with the lumen lined by a peritrophic membrane that is composed of chitin and proteins (peritrophins). The origin of the peritrophins in the midgut of adult bees is unknown. This study used an anti-peritrophin 55-kDa antibody to immunolocalize the sites of the peritrophic membrane synthesis in nine species of adult bees’ representatives of different families and sociability levels. In all studied species the peritrophin-55 is produced by digestive cells in the entire midgut in the rough endoplasmic reticulum following transference to Golgi apparatus and released by secretory vesicles, which fuses with the plasma membrane and microvilli. Thus, in the representatives of different groups of bees, the PM is of type I.
    Full-text · Article · Oct 2014 · Micron
    • "In vertebrates, Goblet cells secrete luminal mucus involved both in the protection of gut lining and the intestinal transit. In Drosophila, the peritrophic membrane (secreted by the ECs) replaces mucus and functions to protect the gut (Kuraishi et al., 2011). Despite these small differences, Drosophila is a convenient model for studying the cellular and molecular mechanisms governing gut homeostasis due to the simplicity of its gut architecture (Shanbhag and Tripathi, 2009), the conservation of the signalling pathways (Vanuytsel et al., 2013; this review) and the multitude of existing tools (Singh et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The digestive tract is subjected to many aggressions throughout animal life. Since disruptions of gut physiology impact on animal fitness and survival, maintenance of gut integrity and functionality is essential for the individual. Over the last 40 years, research on rodents has aimed at understanding how cellular homeostasis of the digestive tract is maintained when challenged with disruptions. Following the discovery of stem cells in the digestive tract of Drosophila, a flurry of studies made an important contribution to our understanding of how the proliferation and the differentiation of these cells are controlled and participate in the renewal of the digestive tract. Insights into these mechanisms in Drosophila have revealed many similarities with mammalian intestinal stem cells. For instance, the highly conserved EGFR, JAK/STAT, Wingless/Wnt, Hedgehog, Integrins, BMP/TGFβ, Hippo and Insulin pathways all participate in adult intestinal cellular homeostasis. Here, we provide a literature review of recent advances in the field highlighting the adult Drosophila midgut as a convenient model for dissecting mechanisms involved in the maintenance of the cellular homeostasis of the digestive tract in conventionally reared conditions. In addition, we shed light on recently published data putting Drosophila forward as a genetic tool to decipher the mechanisms underlying intestinal diseases and intestinal tumour progression.
    No preview · Article · Oct 2014 · Histology and histopathology
  • Source
    • "This phenomenon demonstrates a co-evolving partnership between host and gut microbiota, despite the observation that many of the microbial species in the gut of Drosophila do not colonize the animal permanently, but rather need to be replenished periodically to preserve the composition of the gut flora (Blum et al., 2013). Some microbes may find it difficult to establish permanent communities, possibly as a consequence of epithelial turnover and peritrophic matrix renewal in the midgut (Kuraishi et al., 2011). Additional difficulty could arise via the activity of a broad spectrum of AMPs expressed in each compartment of the gut. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The animal gut serves as a primary location for the complex host-microbe interplay that is essential for homeostasis and may also reflect the types of ancient selective pressures that spawned the emergence of immunity in metazoans. In this review, we present a phylogenetic survey of gut host-microbe interactions and suggest that host defense systems arose not only to protect tissue directly from pathogenic attack but also to actively support growth of specific communities of mutualists. This functional dichotomy resulted in the evolution of immune systems much more tuned for harmonious existence with microbes than previously thought, existing as dynamic but primarily cooperative entities in the present day. We further present the protochordate Ciona intestinalis as a promising model for studying gut host-bacterial dialogue. The taxonomic position, gut physiology and experimental tractability of Ciona offer unique advantages in dissecting host-microbe interplay and can complement studies in other model systems.
    Full-text · Article · Jun 2014 · Developmental & Comparative Immunology
Show more