Plasmodium genetic loci linked to host cytokine and chemokine responses
| Autor: | Sittiporn Pattaradilokrat, Mariam Quinones, Zhao K, Osamu Kaneko, Yanwei Qi, Jiang H, Li N, Zhu J, Carole A. Long, Xin-zhuan Su, Sethu C. Nair, Jian Wu, Jian Li, Richard T. Eastman, Huaman Mc, Martine Zilversmit |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Chemokine
Plasmodium 030231 tropical medicine Immunology Genes Protozoan Quantitative Trait Loci Biology Article 03 medical and health sciences Mice 0302 clinical medicine Genetics medicine cytokine Animals China Genetics (clinical) Chemokine CCL2 Crosses Genetic 030304 developmental biology Mice Knockout 0303 health sciences Polymorphism Genetic pathogenesis chemokine Epistasis Genetic Plasmodium yoelii biology.organism_classification medicine.disease 3. Good health Malaria virulence Disease Models Animal inflammation Genetic Loci Host-Pathogen Interactions biology.protein Cytokines Christian ministry Female genetic mapping Chemokines Genome Protozoan |
| Zdroj: | Genes and immunity |
| ISSN: | 1476-5470 1466-4879 |
| Popis: | Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P0.005) additive effects on IL-1β, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection. |
| Databáze: | OpenAIRE |
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