Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster

Global Health Institute, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 09/2011; 108(38):15966-71. DOI: 10.1073/pnas.1105994108
Source: PubMed

ABSTRACT 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.
    Micron 10/2014; 68. DOI:10.1016/j.micron.2014.09.009 · 2.06 Impact Factor
  • 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.
    Developmental & Comparative Immunology 06/2014; DOI:10.1016/j.dci.2014.06.011 · 3.71 Impact Factor
  • Source
    • "s and toxic compounds , as well as facilitating digestion by partitioning digestive enzymes , ingested food and the cleavage products in the endo - and ectoperitrophic compartments ( Peters , 1992 ) . While the barrier function against infections and toxic compounds has received some attention in several recent studies ( Devenport et al . , 2006 ; Kuraishi et al . , 2011 ; Tomoyasu and Denell , 2004 ) , much less is known about the PM ' s function in facilitating digestion . Digestive enzymes must permeate the PM to reach di - etary molecules in the endoperitrophic space and the intermediate digestion products must cross the PM in the opposite direction to be further processed by enzymes in the ectoperit"
    [Show abstract] [Hide abstract]
    ABSTRACT: The peritrophic matrix (PM) in the midgut of insects consists primarily of chitin and proteins and is thought to support digestion and provide protection from abrasive food particles and enteric pathogens. We examined the physiological roles of 11 putative peritrophic matrix protein (PMP) genes of the red flour beetle, Tribolium castaneum (TcPMPs). TcPMP genes are differentially expressed along the length of the midgut epithelium of feeding larvae. RNAi of individual PMP genes revealed no abnormal developmental phenotypes for 9 of the 11 TcPMPs. However, RNAi for two PMP genes, TcPMP3 and TcPMP5-B, resulted in depletion of the fat body, growth arrest, molting defects and mortality. In situ permeability assays after oral administration of different-sized FITC-dextran beads demonstrated that the exclusion size of the larval peritrophic matrix (PM) decreases progressively from >2 MDa to <4 kDa from the anterior to the most posterior regions of the midgut. In the median midguts of control larvae, 2 MDa dextrans were completely retained within the PM lumen, whereas after RNAi for TcPMP3 and TcPMP5-B, these dextrans penetrated the epithelium of the median midgut, indicating loss of structural integrity and barrier function of the larval PM. In contrast, RNAi for TcPMP5-B, but not RNAi for TcPMP3, resulted in breakdown of impermeability to 4 and 40 kDa dextrans in the PM of the posterior midgut. These results suggest that specific PMPs are involved in the regulation of PM permeability, and that a gradient of barrier function is essential for survival and fat body maintenance.
    Insect biochemistry and molecular biology 03/2014; 49(1). DOI:10.1016/j.ibmb.2014.03.009 · 3.42 Impact Factor
Show more