A Plasmodium-encoded cytokine suppresses T-cell immunity during malaria

Tiffany Sun, Thomas Holowka, Yan Song, Swen Zierow, Lin Leng, Yibang Chen, Huabao Xiong, Jason Griffith, Mehdi Nouraie, Philip E. Thuma, Elias Lolis, Chris J. Janse, Victor R. Gordeuk, Kevin Augustijn, Richard Bucala

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E2117-E2126
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number31
DOIs
StatePublished - Jul 31 2012

Keywords

  • Immune evasion
  • Vaccine

ASJC Scopus subject areas

  • General

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