Functional Genomic Analysis of Midgut Epithelial Responses in Anopheles during Plasmodium Invasion
| Autor: | George K. Christophides, Dina Vlachou, Fotis C. Kafatos, Timm Schlegelmilch |
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| Rok vydání: | 2005 |
| Předmět: |
Plasmodium berghei
Apoptosis Epithelium General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences Immunity RNA interference Anopheles parasitic diseases Hemolymph Animals Cluster Analysis Parasite hosting Oligonucleotide Array Sequence Analysis 030304 developmental biology 0303 health sciences Innate immune system Agricultural and Biological Sciences(all) biology Reverse Transcriptase Polymerase Chain Reaction Biochemistry Genetics and Molecular Biology(all) Gene Expression Profiling fungi 030302 biochemistry & molecular biology Midgut Genomics biology.organism_classification Actins Immunity Innate 3. Good health Cell biology Gene Expression Regulation Immunology RNA Interference General Agricultural and Biological Sciences Digestive System |
| Zdroj: | Current Biology. 15:1185-1195 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2005.06.044 |
| Popis: | Summary Background: The malaria parasite Plasmodium must complete a complex developmental life cycle within Anopheles mosquitoes before it can be transmitted into the human host. One day after mosquito infection, motile ookinetes traverse the midgut epithelium and, after exiting to its basal site facing the hemolymph, develop into oocysts. Previously, we have identified hemolymph factors that can antagonize or promote parasite development. Results: We profiled on a genomic scale the transcriptional responses of the A. gambiae midgut to P. berghei and showed that more than 7% of the assessed mosquito transcriptome is differentially regulated during invasion. The profiles suggested that actin- and microtubule-cytoskeleton remodeling is a major response of the epithelium to ookinete penetration. Other responses encompass components of innate immunity, extracellular-matrix remodeling, and apoptosis. RNAi-dependent gene silencing identified both parasite antagonists and agonists among regulators of actin dynamics and revealed that actin polymerization is inhibitory to the invading parasite. Combined transcriptional and reverse-genetic analysis further identified an unexpected dual role of the lipid-trafficking machinery of the hemolymph for both parasite and mosquito-egg development. Conclusions: We conclude that the determinants of malaria-parasite development in Anopheles include components not only of systemic humoral immunity but also of intracellular, local epithelial reactions. These results provide novel mechanistic insights for understanding malaria transmission in the mosquito vector. |
| Databáze: | OpenAIRE |
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