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

Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2117-26. doi: 10.1073/pnas.1206573109. Epub 2012 Jul 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / genetics
  • Cytokines / immunology*
  • Evolution, Molecular
  • Humans
  • Immunologic Memory / genetics
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / genetics
  • Plasmodium berghei / immunology*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*

Substances

  • Cytokines
  • Proto-Oncogene Proteins c-bcl-2
  • Protozoan Proteins