The Relative Importance of Innate Immune Priming in Wolbachia-Mediated Dengue Interference

Abstract

The non-virulent Wolbachia strain wMel and the life-shortening strain wMelPop-CLA, both originally from Drosophila melanogaster, have been stably introduced into the mosquito vector of dengue fever, Aedes aegypti. Each of these Wolbachia strains interferes with viral pathogenicity and/or dissemination in both their natural Drosophila host and in their new mosquito host, and it has been suggested that this virus interference may be due to host immune priming by Wolbachia. In order to identify aspects of the mosquito immune response that might underpin virus interference, we used whole-genome microarrays to analyse the transcriptional response of A. aegypti to the wMel and wMelPop-CLA Wolbachia strains. While wMel affected the transcription of far fewer host genes than wMelPop-CLA, both strains activated the expression of some immune genes including anti-microbial peptides, Toll pathway genes and genes involved in melanization. Because the induction of these immune genes might be associated with the very recent introduction of Wolbachia into the mosquito, we also examined the same Wolbachia strains in their original host D. melanogaster. First we demonstrated that when dengue viruses were injected into D. melanogaster, virus accumulation was significantly reduced in the presence of Wolbachia, just as in A. aegypti. Second, when we carried out transcriptional analyses of the same immune genes up-regulated in the new heterologous mosquito host in response to Wolbachia we found no over-expression of these genes in D. melanogaster, infected with either wMel or wMelPop. These results reinforce the idea that the fundamental mechanism involved in viral interference in Drosophila and Aedes is not dependent on the up-regulation of the immune effectors examined, although it cannot be excluded that immune priming in the heterologous mosquito host might enhance the virus interference trait.

Implication of the Bacterial Endosymbiont Rickettsia spp. in Interactions of the Whitefly Bemisia tabaci with Tomato yellow leaf curl virus

“…quito Aedes aegypti in Australia and reached near fixation within a few months (38). This is important because Wolbachia has been shown to prime the mosquito innate immune system, thus limiting the ability of pathogens such as dengue virus, Chikungunya virus, and Plasmodium to replicate in mosquito cells (39,40). Limiting the replication of dengue virus in the mosquito vector was shown to be possible using host microRNAs that manipulate host gene expression (41).…”

The Effect of Temperature on Wolbachia-Mediated Dengue Virus Blocking in Aedes aegypti

“…55 Though the fundamental mechanism involved in viral blocking, demonstrated in both Drosophila and Aedes, does not seem to be dependent on the upregulation of the immune effectors, it is likely that Wolbachia-associated immune priming in mosquitoes can enhance the virus blocking phenotype. 56,57 Furthermore, microbial gut flora of mosquito interacts with host immune system to determine the outcome of host-pathogen interactions, 28,58 and evidence is emerging on how temperature can affect the presence and quantity of symbionts in insect's gut to influence host fitness. 59 How different temperature regimes can affect DENV blocking by possibly changing host immunity and its gut microbiota also needs to be investigated.…”

The bacteriumWolbachiaexploits host innate immunity to establish a symbiotic relationship with the dengue vector mosquitoAedes aegypti

“…Activation of the host's innate immune system by Wolbachia has been suggested as one mechanism causing pathogen interference in both naturally infected Drosophila and transinfected A. aegypti mosquitoes (Moreira et al, 2009;Bian et al, 2010;Rances et al, 2012;Wong et al, 2015), but the impact on Wolbachia itself has remained unclear. In this work, we have shown that both the IMD and Toll pathways in A. aegypti are triggered by introduction of the bacterium Wolbachia wAlbB.…”