Plasmodium Strain Determines Dendritic Cell Function Essential for Survival from Malaria

PLoS Pathogens

Michael F Good¹  Danielle I Stanisic²  Mark J Smyth³  Ranjeny Thomas⁴  Lynette Beattie⁵  Michelle N Wykes⁵  Xue Q Liu⁵  Katryn J Stacey⁵ 

[1] Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia;Immunology and Infection Unit, University of York, York, United Kingdom;Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;Institute for Molecular Bioscience, CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane, Queensland, Australia;The Queensland Institute of Medical Research, Brisbane, Queensland, Australia

关键词: Plasmodium yoelii;    Parasitic diseases;    T cells;    Spleen;    Malaria;    Immune response;    Malarial parasites;    Cytokines;   

DOI  :  10.1371/journal.ppat.0030096

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. However, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. Identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. Since immunity is initiated by dendritic cells (DCs), we compared their phenotype and function following infection with either a nonlethal or lethal strain of the rodent parasite, Plasmodium yoelii, to identify their contribution to disease severity. DCs from nonlethal infections were fully functional and capable of secreting cytokines and stimulating T cells. In contrast, DCs from lethal infections were not functional. We then transferred DCs from mice with nonlethal infections to mice given lethal infections and showed that these DCs mediated control of parasitemia and survival. IL-12 was necessary for survival. To our knowledge, our studies have shown for the first time that during a malaria infection, DC function is essential for survival. More importantly, the functions of these DCs are determined by the strain of parasite. Our studies may explain, in part, why natural malaria infections may have different outcomes.

【 授权许可】

CC BY