Plasmodium strain determines dendritic cell function essential for survival from malaria

• Published in: PLoS pathogens Vol. 3; no. 7; p. e96
• Main Authors: Wykes, Michelle N, Liu, Xue Q, Beattie, Lynette, Stanisic, Danielle I, Stacey, Katryn J, Smyth, Mark J, Thomas, Ranjeny, Good, Michael F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2007; Public Library of Science (PLoS)
• Subjects: Adoptive Transfer; Animals; Blood; Cell Count; Cytokines; Dendritic cells; Dendritic Cells - physiology; Disease; Disease Models, Animal; Disease Susceptibility; Experiments; Female; Flow Cytometry; Host-Parasite Interactions; Immune system; Immune Tolerance - genetics; Immunology; Infectious Diseases; Interferon-alpha - metabolism; Interleukin-12 - metabolism; Longevity; Lymphocytes; Malaria; Malaria - immunology; Malaria - parasitology; Mice; Mice, Inbred C57BL; Microbiology; Mus (Mouse); None; Parasitemia - immunology; Parasites; Phenotype; Plasmodium; Plasmodium yoelii - classification; Plasmodium yoelii - immunology; Plasmodium yoelii - pathogenicity; Properties; Rodents; Specific Pathogen-Free Organisms; Spleen - cytology; Spleen - immunology; Spleen - parasitology; Studies; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.0030096

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.