A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence

Murad R. Mamedov, Anja Scholzen, Ramesh V. Nair, Katherine Cumnock, Justin A. Kenkel, Jose Henrique M. Oliveira, Damian L. Trujillo, Naresha Saligrama, Yue Zhang, Florian Rubelt, David S. Schneider, Yueh hsiu Chien, Robert W. Sauerwein, Mark M. Davis

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Despite evidence that γδ T cells play an important role during malaria, their precise role remains unclear. During murine malaria induced by Plasmodium chabaudi infection and in human P. falciparum infection, we found that γδ T cells expanded rapidly after resolution of acute parasitemia, in contrast to αβ T cells that expanded at the acute stage and then declined. Single-cell sequencing showed that TRAV15N-1 (Vδ6.3) γδ T cells were clonally expanded in mice and had convergent complementarity-determining region 3 sequences. These γδ T cells expressed specific cytokines, M-CSF, CCL5, CCL3, which are known to act on myeloid cells, indicating that this γδ T cell subset might have distinct functions. Both γδ T cells and M-CSF were necessary for preventing parasitemic recurrence. These findings point to an M-CSF-producing γδ T cell subset that fulfills a specialized protective role in the later stage of malaria infection when αβ T cells have declined. γδ T cell frequency increases late during mouse and human malaria. Mamedov et al. show that oligoclonal TRAV15N-1 (Vδ6.3) γδ T cells expand across various tissues and prevent late-stage parasitemic recurrence. These protective γδ T cells exhibit a distinct transcriptional profile that includes abundantly expressed M-CSF, which protects against Plasmodium recurrence.

Original languageEnglish
Pages (from-to)350-363.e7
JournalImmunity
Volume48
Issue number2
DOIs
StatePublished - Feb 20 2018

Keywords

  • M-CSF
  • Plasmodium chabaudi
  • Plasmodium falciparum
  • TRAV15N-1
  • TγδM
  • Vδ6.3
  • gamma-delta T cells
  • malaria
  • recrudescence
  • γδ T cells

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