A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria.
The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2-associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Tiffany
T
Sun
Thomas
T
Holowka
Yan
Y
Song
Swen
S
Zierow
Lin
L
Leng
Yibang
Y
Chen
Huabao
H
Xiong
Jason
J
Griffith
Mehdi
M
Nouraie
Philip E
PE
Thuma
Elias
E
Lolis
Chris J
CJ
Janse
Victor R
VR
Gordeuk
Kevin
K
Augustijn
Richard
R
Bucala
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D015800:Protozoan Proteins