title: MicroRNA-regulation of Anopheles gambiae immunity to Plasmodium falciparum infection and midgut microbiota.
abstract: Invasion of the malaria vector Anopheles gambiae midgut by Plasmodium parasites triggers transcriptional changes of immune genes that mediate the antiparasitic defense. This response is largely regulated by the Toll and Immune deficiency (IMD) pathways. To determine whether A. gambiae microRNAs (miRNAs) are involved in regulating the anti-Plasmodium defense, we showed that suppression of miRNA biogenesis results in increased resistance to Plasmodium falciparum infection. In silico analysis of A. gambiae immune effector genes identified multiple transcripts with miRNA binding sites. A comparative miRNA microarray abundance analysis of P. falciparum infected and naïve mosquito midgut tissues showed elevated abundance of miRNAs aga-miR-989 and aga-miR-305 in infected midguts. Antagomir inhibition of aga-miR-305 increased resistance to P. falciparum infection and suppressed the midgut microbiota. Conversely, treatment of mosquitoes with an artificial aga-miR-305 mimic increased susceptibility to P. falciparum infection and resulted in expansion of midgut microbiota, suggesting that aga-miR-305 acts as a P. falciparum and gut microbiota agonist by negatively regulating the mosquito immune response. In silico prediction of aga-miR-305 target genes identified several anti-Plasmodium effectors. Our study shows that A. gambiae aga-miR-305 regulates the anti-Plasmodium response and midgut microbiota, likely through post-transcriptional modification of immune effector genes.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Dennison
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Omar J
authors.initials: OJ
authors.lastname: BenMarzouk-Hidalgo
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: gdimopo1@jhu.edu.
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000852:Anopheles / Q000276:immunology* / Q000469:parasitology; D004064:Digestive System / Q000276:immunology* / Q000382:microbiology; D006790:Host-Parasite Interactions / Q000276:immunology; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology; D007303:Insect Vectors / Q000276:immunology* / Q000469:parasitology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D064307:Microbiota / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000502:physiology; D034622:RNA Interference / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D019476:Insect Proteins; D035683:MicroRNAs
keywords: Anopheles gambiae; Immunity; MicroRNAs; Microbiota; Plasmodium