Dataset Information

Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions.

ABSTRACT:

Background

Parasite biology, by its very nature, cannot be understood without integrating it with that of the host, nor can the host response be adequately explained without considering the activity of the parasite. However, due to experimental limitations, molecular studies of parasite-host systems have been predominantly one-sided investigations focusing on either of the partners involved. Here, we conducted a dual RNA-seq time course analysis of filarial worm parasite and host mosquito to better understand the parasite processes underlying development in and interaction with the host tissue, from the establishment of infection to the development of infective-stage larva.

Methodology/principal findings

Using the Brugia malayi-Aedes aegypti system, we report parasite gene transcription dynamics, which exhibited a highly ordered developmental program consisting of a series of cyclical and state-transitioning temporal patterns. In addition, we contextualized these parasite data in relation to the concurrent dynamics of the host transcriptome. Comparative analyses using uninfected tissues and different host strains revealed the influence of parasite development on host gene transcription as well as the influence of the host environment on parasite gene transcription. We also critically evaluated the life-cycle transcriptome of B. malayi by comparing developmental stages in the mosquito relative to those in the mammalian host, providing insight into gene expression changes underpinning the mosquito-borne parasitic lifestyle of this heteroxenous parasite.

Conclusions/significance

The data presented herein provide the research community with information to design wet lab experiments and select candidates for future study to more fully dissect the whole set of molecular interactions of both organisms in this mosquito-filarial worm symbiotic relationship. Furthermore, characterization of the transcriptional program over the complete life cycle of the parasite, including stages within the mosquito, could help devise novel targets for control strategies.

SUBMITTER: Choi YJ

PROVIDER: S-EPMC4031193 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions.

Choi Young-Jun YJ Aliota Matthew T MT Mayhew George F GF Erickson Sara M SM Christensen Bruce M BM

PLoS neglected tropical diseases 20140522 5

<h4>Background</h4>Parasite biology, by its very nature, cannot be understood without integrating it with that of the host, nor can the host response be adequately explained without considering the activity of the parasite. However, due to experimental limitations, molecular studies of parasite-host systems have been predominantly one-sided investigations focusing on either of the partners involved. Here, we conducted a dual RNA-seq time course analysis of filarial worm parasite and host mosquit ...[more]

PMID: 24853112

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Project description:Armigeres subalbatus is a natural vector of the filarial worm Brugia pahangi, but it kills Brugia malayi microfilariae (mf) by melanotic encapsulation. Because B. malayi and B. pahangi are morphologically and biologically similar, this mosquito-parasite system serves as a valuable model for studying resistance mechanisms in mosquito vectors. Comparing Ar. subalbatus-B. pahangi susceptibility and Ar. subalbatus-B. malayi refractoriness could provide significant insight into recognition mechanisms required to mount an effective anti-filarial worm immune response in the mosquito, as well as provide considerable detail into the molecular components involved in vector competence. Accordingly, we initiated transcriptome profiling studies of Ar. subalbatus in relation to filarial worm infection to provide information on the molecular components involved in B. pahangi susceptibility for comparison with our earlier studies on B. malayi refractoriness (Aliota et al., 2007). In addition, these studies also provide information on the infection response of a natural vector, i.e., the overall transcriptional and physiological change that occurs in the mosquito as a result of parasite infection, for comparison with our previous studies that employed a highly susceptible laboratory model, Aedes aegypti (Erickson et al., 2009). The time course chosen facilitated an examination of key events in the development of the parasite, beginning with the very start of filarial worm infection and spanning to well after infective-stage parasites had completed development in the mosquito. Herein, we demonstrate that filarial worm susceptibility in Ar. subalbatus is a highly complex process during the first 24 hours of infection. It is a process that involves many factors of both known and unknown function which are most likely associated with filarial worm penetration through the midgut lumen, invasion into thoracic muscle cells, and maintenance of homeostasis in the hemolymph environment. The data show that there are distinct and separate transcriptional patterns associated with filarial worm susceptibility as compared to refractoriness, and that an infection response in Ar. subalbatus, a natural vector, can differ significantly from that observed in Ae. aegypti, a common laboratory model. Finally, the data presented herein provide us with a cadre of information to design wet lab experiments and select candidates for further study to more fully dissect the nature of the anti-filarial worm immune response in this mosquito-parasite system.

Project description:BackgroundArmigeres subalbatus is a natural vector of the filarial worm Brugia pahangi, but it kills Brugia malayi microfilariae by melanotic encapsulation. Because B. malayi and B. pahangi are morphologically and biologically similar, comparing Ar. subalbatus-B. pahangi susceptibility and Ar. subalbatus-B. malayi refractoriness could provide significant insight into recognition mechanisms required to mount an effective anti-filarial worm immune response in the mosquito, as well as provide considerable detail into the molecular components involved in vector competence. Previously, we assessed the transcriptional response of Ar. subalbatus to B. malayi, and now we report transcriptome profiling studies of Ar. subalbatus in relation to filarial worm infection to provide information on the molecular components involved in B. pahangi susceptibility.Methodology/principal findingsUtilizing microarrays, comparisons were made between mosquitoes exposed to B. pahangi, B. malayi, and uninfected bloodmeals. The time course chosen facilitated an examination of key events in the development of the parasite, beginning with the very start of filarial worm infection and spanning to well after parasites had developed to the infective stage in the mosquito. At 1, 3, 6, 12, 24 h post infection and 2-3, 5-6, 8-9, and 13-14 days post challenge there were 31, 75, 113, 76, 54, 5, 3, 13, and 2 detectable transcripts, respectively, with significant differences in transcript abundance (increase or decrease) as a result of parasite development.Conclusions/significanceHerein, we demonstrate that filarial worm susceptibility in a laboratory strain of the natural vector Ar. subalbatus involves many factors of both known and unknown function that most likely are associated with filarial worm penetration through the midgut, invasion into thoracic muscle cells, and maintenance of homeostasis in the hemolymph environment. The data show that there are distinct and separate transcriptional patterns associated with filarial worm susceptibility as compared to refractoriness, and that an infection response in Ar. subalbatus can differ significantly from that observed in Ae. aegypti, a common laboratory model.

Project description:Dual RNA sequencing (RNA-Seq) is the simultaneous transcriptomic analysis of interacting symbionts, for example, in malaria. Potential cross-species interactions identified by correlated gene expression might highlight interlinked signaling, metabolic, or gene regulatory pathways in addition to physically interacting proteins. Often, malaria studies address one of the interacting organisms-host or parasite-rendering the other "contamination." Here we perform a meta-analysis using such studies for cross-species expression analysis. We screened experiments for gene expression from host and Plasmodium. Out of 171 studies in Homo sapiens, Macaca mulatta, and Mus musculus, we identified 63 potential studies containing host and parasite data. While 16 studies (1,950 samples) explicitly performed dual RNA-Seq, 47 (1,398 samples) originally focused on one organism. We found 915 experimental replicates from 20 blood studies to be suitable for coexpression analysis and used orthologs for meta-analysis across different host-parasite systems. Centrality metrics from the derived gene expression networks correlated with gene essentiality in the parasites. We found indications of host immune response to elements of the Plasmodium protein degradation system, an antimalarial drug target. We identified well-studied immune responses in the host with our coexpression networks, as our approach recovers known broad processes interlinked between hosts and parasites in addition to individual host and parasite protein associations. The set of core interactions represents commonalities between human malaria and its model systems for prioritization in laboratory experiments. Our approach might also allow insights into the transferability of model systems for different pathways in malaria studies.IMPORTANCE Malaria still causes about 400,000 deaths a year and is one of the most studied infectious diseases. The disease is studied in mice and monkeys as lab models to derive potential therapeutic intervention in human malaria. Interactions between Plasmodium spp. and its hosts are either conserved across different host-parasite systems or idiosyncratic to those systems. Here we use correlation of gene expression from different RNA-Seq studies to infer common host-parasite interactions across human, mouse, and monkey studies. First, we find a set of very conserved interactors, worth further scrutiny in focused laboratory experiments. Second, this work might help assess to which extent experiments and knowledge on different pathways can be transferred from models to humans for potential therapy.

Project description:BackgroundParasites can either respond to differences in immune defenses that exist between individual hosts plastically or, alternatively, follow a genetically canalized ("hard wired") program of infection. Assuming that large-scale functional plasticity would be discernible in the parasite transcriptome we have performed a dual RNA-seq study of the lifecycle of Eimeria falciformis using infected mice with different immune status as models for coccidian infections.ResultsWe compared parasite and host transcriptomes (dual transcriptome) between naïve and challenge infected mice, as well as between immune competent and immune deficient ones. Mice with different immune competence show transcriptional differences as well as differences in parasite reproduction (oocyst shedding). Broad gene categories represented by differently abundant host genes indicate enrichments for immune reaction and tissue repair functions. More specifically, TGF-beta, EGF, TNF and IL-1 and IL-6 are examples of functional annotations represented differently depending on host immune status. Much in contrast, parasite transcriptomes were neither different between Coccidia isolated from immune competent and immune deficient mice, nor between those harvested from naïve and challenge infected mice. Instead, parasite transcriptomes have distinct profiles early and late in infection, characterized largely by biosynthesis or motility associated functional gene groups, respectively. Extracellular sporozoite and oocyst stages showed distinct transcriptional profiles and sporozoite transcriptomes were found enriched for species specific genes and likely pathogenicity factors.ConclusionWe propose that the niche and host-specific parasite E. falciformis uses a genetically canalized program of infection. This program is likely fixed in an evolutionary process rather than employing phenotypic plasticity to interact with its host. This in turn might limit the potential of the parasite to adapt to new host species or niches, forcing it to coevolve with its host.

Dataset Information

Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions.

Background

Methodology/principal findings

Conclusions/significance

Publications

Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions.

Similar Datasets

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