R T Eastman

National Institutes of Health

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H-Index

i-10 index

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Hongying Jiang

China International Science and Technology Cooperation

Keji Zhao

National Heart Lung and Blood Institute

Xin‐zhuan Su

National Institutes of Health

Martine Zilversmit

National Institutes of Health

S C Nair

National Institutes of Health

Na Li

Nankai University

Junjie Zhu

National Heart Lung and Blood Institute

C A Long

National Institutes of Health

Sittiporn Pattaradilokrat

Chulalongkorn University

Osamu Kaneko

Nagasaki University

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National Institutes of Health

National Institute of Allergy and Infectious Diseases

Kunming Medical University

National Heart Lung and Blood Institute

Lanzhou University

Osaka University

Peking University

Chinese Academy of Sciences

China International Science and Technology Cooperation

Army Medical University

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Plasmodium genetic loci linked to host cytokine and chemokine responses

Genes and Immunity (2014)

Sittiporn Pattaradilokrat Jian Li Jianhua Wu Y Qi R T Eastman

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.

Plasmodium yoelii

Pathogenesis

10.1038/gene.2013.74

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