title: A dityrosine network mediated by dual oxidase and peroxidase influences the persistence of Lyme disease pathogens within the vector.
abstract: Ixodes scapularis ticks transmit a wide array of human and animal pathogens including Borrelia burgdorferi; however, how tick immune components influence the persistence of invading pathogens remains unknown. As originally demonstrated in Caenorhabditis elegans and later in Anopheles gambiae, we show here that an acellular gut barrier, resulting from the tyrosine cross-linking of the extracellular matrix, also exists in I. scapularis ticks. This dityrosine network (DTN) is dependent upon a dual oxidase (Duox), which is a member of the NADPH oxidase family. The Ixodes genome encodes for a single Duox and at least 16 potential peroxidase proteins, one of which, annotated as ISCW017368, together with Duox has been found to be indispensible for DTN formation. This barrier influences pathogen survival in the gut, as an impaired DTN in Doux knockdown or in specific peroxidase knockdown ticks, results in reduced levels of B. burgdorferi persistence within ticks. Absence of a complete DTN formation in knockdown ticks leads to the activation of specific tick innate immune pathway genes that potentially resulted in the reduction of spirochete levels. Together, these results highlighted the evolution of the DTN in a diverse set of arthropod vectors, including ticks, and its role in protecting invading pathogens like B. burgdorferi. Further understanding of the molecular basis of tick innate immune responses, vector-pathogen interaction, and their contributions in microbial persistence may help the development of new targets for disrupting the pathogen life cycle.
authors.affiliation: From the Department of Veterinary Medicine and Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742 and.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Yang
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Smith
authors.forename: Mark S
authors.initials: MS
authors.lastname: Williams
authors.forename: Utpal
authors.initials: U
authors.lastname: Pal
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000235:genetics / Q000378:metabolism*; D001179:Arthropod Vectors / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D025065:Borrelia burgdorferi / Q000254:growth & development / Q000502:physiology; D041981:Gastrointestinal Tract / Q000382:microbiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018884:Ixodes / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D008193:Lyme Disease / Q000382:microbiology / Q000469:parasitology; D051379:Mice; D008809:Mice, Inbred C3H; D050296:Microbial Viability / Q000235:genetics; D018613:Microscopy, Confocal; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism
chemical_list: D060829:Arthropod Proteins; D014443:Tyrosine; C007543:dityrosine; D009195:Peroxidase; D019255:NADPH Oxidases
keywords: Host-Pathogen Interactions; Infectious Diseases; Innate Immunity; Microbiology; NADPH Oxidase; Nitric-oxide Synthase; Peroxidase; Protein Cross-linking