Transcriptional Memory-Like Imprints and Enhanced Functional Activity in γδ T Cells Following Resolution of Malaria Infection

Rasika Kumarasingha; Lisa J Ioannidis; Waruni Abeysekera; Stephanie Studniberg; Dinidu Wijesurendra; Ramin Mazhari; Daniel P Poole; Ivo Mueller; Louis Schofield; Diana S Hansen; Emily M Eriksson

doi:10.3389/fimmu.2020.582358

Transcriptional Memory-Like Imprints and Enhanced Functional Activity in γδ T Cells Following Resolution of Malaria Infection

Front Immunol. 2020 Oct 14:11:582358. doi: 10.3389/fimmu.2020.582358. eCollection 2020.

Authors

Rasika Kumarasingha^{1

2}, Lisa J Ioannidis^{1

2}, Waruni Abeysekera^{1

2}, Stephanie Studniberg^{1

2}, Dinidu Wijesurendra^{1

2}, Ramin Mazhari^{1

2}, Daniel P Poole³, Ivo Mueller^{1

2}, Louis Schofield^{1

4

5}, Diana S Hansen^{1

2}, Emily M Eriksson^{1

2}

Affiliations

¹ Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
² Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.
³ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
⁴ School of Veterinary and Biomedical Sciences, James Cook University, Townsville, QLD, Australia.
⁵ Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, QLD, Australia.

Abstract

γδ T cells play an essential role in the immune response to many pathogens, including Plasmodium. However, long-lasting effects of infection on the γδ T cell population still remain inadequately understood. This study focused on assessing molecular and functional changes that persist in the γδ T cell population following resolution of malaria infection. We investigated transcriptional changes and memory-like functional capacity of malaria pre-exposed γδ T cells using a Plasmodiumchabaudi infection model. We show that multiple genes associated with effector function (chemokines, cytokines and cytotoxicity) and antigen-presentation were upregulated in P. chabaudi-exposed γδ T cells compared to γδ T cells from naïve mice. This transcriptional profile was positively correlated with profiles observed in conventional memory CD8⁺ T cells and was accompanied by enhanced reactivation upon secondary encounter with Plasmodium-infected red blood cells in vitro. Collectively our data demonstrate that Plasmodium exposure result in "memory-like imprints" in the γδ T cell population and also promotes γδ T cells that can support antigen-presentation during subsequent infections.

Keywords: Plasmodium; RNA-Seq; chabaudi; memory; γδ T cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen Presentation
Cells, Cultured
Disease Models, Animal
Female
Gene Expression Regulation
Humans
Immunologic Memory
Lymphocyte Activation
Malaria / immunology*
Mice
Mice, Inbred C57BL
Plasmodium chabaudi / physiology*
Receptors, Antigen, T-Cell, gamma-delta / metabolism
T-Lymphocytes / immunology*

Substances

Receptors, Antigen, T-Cell, gamma-delta