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Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion.
Curr Biol. 2005 Jul 12; 15(13):1185-95.CB

Abstract

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.

Authors+Show Affiliations

European Molecular Biology Laboratory, Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16005290

Citation

Vlachou, Dina, et al. "Functional Genomic Analysis of Midgut Epithelial Responses in Anopheles During Plasmodium Invasion." Current Biology : CB, vol. 15, no. 13, 2005, pp. 1185-95.
Vlachou D, Schlegelmilch T, Christophides GK, et al. Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. Curr Biol. 2005;15(13):1185-95.
Vlachou, D., Schlegelmilch, T., Christophides, G. K., & Kafatos, F. C. (2005). Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. Current Biology : CB, 15(13), 1185-95.
Vlachou D, et al. Functional Genomic Analysis of Midgut Epithelial Responses in Anopheles During Plasmodium Invasion. Curr Biol. 2005 Jul 12;15(13):1185-95. PubMed PMID: 16005290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. AU - Vlachou,Dina, AU - Schlegelmilch,Timm, AU - Christophides,George K, AU - Kafatos,Fotis C, PY - 2005/04/19/received PY - 2005/06/03/revised PY - 2005/06/07/accepted PY - 2005/7/12/pubmed PY - 2005/9/30/medline PY - 2005/7/12/entrez SP - 1185 EP - 95 JF - Current biology : CB JO - Curr. Biol. VL - 15 IS - 13 N2 - 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. SN - 0960-9822 UR - https://www.unboundmedicine.com/medline/citation/16005290/Functional_genomic_analysis_of_midgut_epithelial_responses_in_Anopheles_during_Plasmodium_invasion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(05)00679-2 DB - PRIME DP - Unbound Medicine ER -