A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae.
Extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that a peroxidase, secreted by the Anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. This network protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Sanjeev
S
Kumar
Alvaro
A
Molina-Cruz
Lalita
L
Gupta
Janneth
J
Rodrigues
Carolina
C
Barillas-Mury
D000818:Animals; D000852:Anopheles / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000276:immunology; D018407:Bacterial Physiological Phenomena; D001769:Blood; D004064:Digestive System / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D019476:Insect Proteins / Q000378:metabolism; D008954:Models, Biological; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D010539:Permeability; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism*; D010962:Plasmodium berghei / Q000276:immunology / Q000502:physiology; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology; D034622:RNA Interference; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000900:Anti-Bacterial Agents; D019476:Insect Proteins; D014443:Tyrosine; C007543:dityrosine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases