Prostaglandins regulate humoral immune responses in Aedes aegypti.

Prostaglandins (PGs) are immuno-active lipids that mediate the immune response in invertebrates and vertebrates. In insects, PGs play a role on different physiological processes such as reproduction, ion transport and regulation of cellular immunity. However, it is unclear whether PGs play a role in invertebrate's humoral immunity, and, if so, which immune signaling pathways would be modulated by PGs. Here, we show that Aedes aegypti gut microbiota and Gram-negative bacteria challenge induces prostaglandin production sensitive to an irreversible inhibitor of the vertebrate cyclooxygenase, acetylsalicylic acid (ASA). ASA treatment reduced PG synthesis and is associated with decreased expression of components of the Toll and IMD immune pathways, thereby rendering mosquitoes more susceptible to both bacterial and viral infections. We also shown that a cytosolic phospholipase (PLAc), one of the upstream regulators of PG synthesis, is induced by the microbiota in the midgut after blood feeding. The knockdown of the PLAc decreased prostaglandin production and enhanced the replication of Dengue in the midgut. We conclude that in Ae. aegypti, PGs control the amplitude of the immune response to guarantee an efficient pathogen clearance

Microbiota activates IMD pathway and limits Sindbis infection in Aedes aegypti

Submitted by Sandra Infurna ([email protected]) on 2017-03-07T12:09:56Z No. of bitstreams: 1 luiza_pereira_etal_IOC_2017.pdf: 946502 bytes, checksum: 9fbc3fe71c26955f1174456ceca1c987 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-03-07T12:21:23Z (GMT) No. of bitstreams: 1 luiza_pereira_etal_IOC_2017.pdf: 946502 bytes, checksum: 9fbc3fe71c26955f1174456ceca1c987 (MD5)Made available in DSpace on 2017-03-07T12:21:23Z (GMT). No. of bitstreams: 1 luiza_pereira_etal_IOC_2017.pdf: 946502 bytes, checksum: 9fbc3fe71c26955f1174456ceca1c987 (MD5) Previous issue date: 2017Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas em Leishmaniose. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil.Background: 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. Results: 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. Conclusion: 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