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Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection

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Publication
https://doi.org/10.1038/s41467-018-06978-5
Domain
Life & Health Sciences
Fellow
William Horsnell

Nature Communications volume 9, Article number: 4516 (2018)

Marion Rolot1, Annette M. Dougall1, Alisha Chetty2, Justine Javaux1, Ting Chen1, Xue Xiao1, Bénédicte Machiels1, Murray E. Selkirk3, Rick M. Maizels4, Cornelis Hokke5, Olivier Denis6, Frank Brombacher2,7,8,
Alain Vanderplasschen1, Laurent Gillet1, William G. C. Horsnell2,9,10 & Benjamin G. Dewals1

 

1 Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine – FARAH, University of Liège, Avenue de Cureghem 10, 4000 Liège, Belgium.

2 Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa 7925.

3 Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

4 Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.

5 Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

6 Scientific Institute of Public Health, Immunology, Communicable and Infectious Diseases, Rue Engeland 642, 1180 Brussels, Belgium.

7 International Centre for Genetic Engineering and Biotechnology, 7925 Cape Town, South Africa.

8 South African Medical Research Council (SAMRC), 7925 Cape Town, South Africa.

9 Institute of Microbiology and Infection, University of Birmingham, B15 2TT Birmingham, UK.

10 Laboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans Le Studium Institute for Advanced Studies, Rue Dupanloup, 45000 Orléans, France.

These authors contributed equally: Marion Rolot, Annette M. Dougall.
Correspondence and requests for materials should be addressed to B.G.D. (email: bgdewals@uliege.be)

Abstract

Infection with parasitic helminths can imprint the immune system to modulate bystander inflammatory processes. Bystander or virtual memory CD8+ T cells (TVM) are non-conventional T cells displaying memory properties that can be generated through responsiveness to interleukin (IL)-4. However, it is not clear if helminth-induced type 2 immunity functionally affects the TVM compartment. Here, we show that helminths expand CD44hiCD62LhiCXCR3hiCD49dlo TVM cells through direct IL-4 signaling in CD8+ T cells. Importantly, helminth-mediated conditioning of TVM cells provided enhanced control of acute respiratory infection with the murid gammaherpesvirus 4 (MuHV-4). This enhanced control of MuHV-4 infection could further be explained by an increase in antigen-specific CD8+ T cell effector responses in the lung and was directly dependent on IL-4 signaling. These results demonstrate that IL-4 during helminth infection can non-specifically condition CD8+ T cells, leading to a subsequently raised antigen-specific CD8+ T cell activation that enhances control of viral infection.

Keywords

CD8-positive T cells
Infection
Parasitic infection
Viral infection
Published by

Nature