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

doi:10.1016/j.immuni.2018.01.009

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

Immunity. 2018 Feb 20;48(2):350-363.e7. doi: 10.1016/j.immuni.2018.01.009. Epub 2018 Feb 6.

Authors

Affiliations

¹ Program in Immunology, Stanford University, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
² Department of Medical Microbiology, Radboud University Medical Center, 6500 HB, Nijmegen, the Netherlands; Innatoss Laboratories B.V., 5349 AB Oss, the Netherlands.
³ Department of Genetics, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
⁵ Department of Pathology, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Brazil.
⁷ Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Aduro Biotech, Inc., Berkeley, CA 94710, USA.
⁸ Department of Genetics, Stanford University, Stanford, CA 94305, USA; Genetics Bioinformatics Service Center, Stanford University, Stanford, CA 94305, USA.
⁹ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
¹⁰ Program in Immunology, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
¹¹ Department of Medical Microbiology, Radboud University Medical Center, 6500 HB, Nijmegen, the Netherlands.
¹² Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: mmdavis@stanford.edu.

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.

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

Publication types

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

MeSH terms

Animals
Female
Humans
Lymphocyte Activation
Macrophage Colony-Stimulating Factor / physiology*
Malaria / immunology
Malaria / prevention & control*
Mice
Parasitemia / prevention & control
Receptors, Antigen, T-Cell, gamma-delta / physiology*
Recurrence
T-Lymphocyte Subsets / immunology*

Substances

Receptors, Antigen, T-Cell, gamma-delta
Macrophage Colony-Stimulating Factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding