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Plasmodium genetic loci linked to host cytokine and chemokine responses

Genes & Immunity volume 15, pages 145–152 (2014)Cite this article

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Abstract

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 (P<0.005) 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.

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Acknowledgements

We thank Drs Alan Sher and David Sacks for valuable advice and comments and Brenda Rae Marshall, DPSS, NIAID, for editing. This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and partially by ‘Project 111’ sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (B06016) and by the National Natural Science Foundation of China (#81271858, #81201324 and #81220108019).

As SP, JL, JW, YQ, RTE, MZ, SCN, MCH, MQ, HJ, JZ, KZ, CAL and X-zS are government employees and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the NIH reserves the right to provide the work to PubMedCentral for display and use by the public, and PubMedCentral may tag or modify the work consistent with its customary practices. You can establish rights outside of the US subject to a government use license.

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Authors and Affiliations

  1. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA

    S Pattaradilokrat, J Li, J Wu, Y Qi, R T Eastman, M Zilversmit, S C Nair, M C Huaman, H Jiang, C A Long & X-z Su

  2. Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand

    S Pattaradilokrat

  3. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P. R. China

    J Li & Y Qi

  4. Advanced Bioscience Laboratories, Medical Center Drive, Rockville, MD, USA

    M C Huaman

  5. Bioinformatics and Computational Biosciences Branch, NIAID, NIH, Bethesda, MD, USA

    M Quinones

  6. General Health Science, US Food and Drug Administration, Silver Spring, MD, USA

    H Jiang

  7. MedImmune, Gaithersburg, MD, USA

    N Li

  8. Genetics and Developmental Biology Center, NIH, Bethesda, MD, USA

    J Zhu

  9. Systems Biology Center, National Heart Lung and Blood Institute, NIH, Bethesda, MD, USA

    K Zhao

  10. Department of Protozoology, Institute of Tropical Medicine and the Global Center of Excellence Program, Nagasaki University, Nagasaki, Japan

    O Kaneko

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Pattaradilokrat, S., Li, J., Wu, J. et al. Plasmodium genetic loci linked to host cytokine and chemokine responses. Genes Immun 15, 145–152 (2014). https://doi.org/10.1038/gene.2013.74

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