title: Microbiota activates IMD pathway and limits Sindbis infection in Aedes aegypti.
abstract: Aedes aegypti is the main vector of important arboviruses such as dengue, Zika and chikungunya. During infections mosquitoes can activate the immune pathways Toll, IMD and JAK/STAT to limit pathogen replication.
  
  
  
  Here, we evaluate the immune response profile of Ae. aegypti against Sindbis virus (SINV). We analyzed gene expression of components of Toll, IMD and JAK/STAT pathways and showed that a blood meal and virus infection upregulated aaREL2 in a microbiota-dependent fashion, since this induction was prevented by antibiotic. The presence of the microbiota activates IMD and impaired the replication of SINV in the midgut. Constitutive activation of the IMD pathway, by Caspar depletion, leads to a decrease in microbiota levels and an increase in SINV loads.
  
  
  
  Together, these results suggest that a blood meal is able to activate innate immune pathways, through a nutrient induced growth of microbiota, leading to upregulation of aaREL2 and IMD activation. Microbiota levels seemed to have a reciprocal interaction, where the proliferation of the microbiota activates IMD pathway that in turn controls bacterial levels, allowing SINV replication in Ae. aegypti mosquitoes. The activation of the IMD pathway seems to have an indirect effect in SINV levels that is induced by the microbiota.
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. barletta@bioqmed.ufrj.br.
authors.forename: Ana Beatriz Ferreira
authors.initials: AB
authors.lastname: Barletta
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Maria Clara L
authors.initials: MC
authors.lastname: Nascimento-Silva
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Octávio A C
authors.initials: OA
authors.lastname: Talyuli
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: José Henrique M
authors.initials: JH
authors.lastname: Oliveira
authors.affiliation: Laboratório de Pesquisas em Leishmaniose, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Luiza Oliveira Ramos
authors.initials: LO
authors.lastname: Pereira
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Oliveira
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Marcos Henrique F
authors.initials: MH
authors.lastname: Sorgine
mesh_terms: D000330:Aedes / Q000276:immunology / Q000821:virology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology*; D054884:Host-Pathogen Interactions; D064307:Microbiota / Q000187:drug effects / Q000502:physiology*; D010406:Penicillins / Q000494:pharmacology; D012845:Sindbis Virus / Q000502:physiology*; D013307:Streptomycin / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D013307:Streptomycin
keywords: Aedes aegypti; IMD; Immune response; Microbiota; Sindbis virus