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

Rolot, M. et al. (2018) Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection. Nature Communications, 9, 4516. (doi: 10.1038/s41467-018-06978-5) (PMID:30375396) (PMCID:PMC6207712)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maizels, Professor Rick
• Authors: Rolot, M., Dougall, A. M., Chetty, A., Javaux, J., Chen, T., Xiao, X., Machiels, B., Selkirk, M. E., Maizels, R. M., Hokke, C., Denis, O., Brombacher, F., Vanderplasschen, A., Gillet, L., Horsnell, W. G. C., and Dewals, B. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Published Online: 30 October 2018
• First Published: First published in Nature Communications 9:4516
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173801		Helminths and the Immune System: Regulation, Regulators and Immunity	Richard Maizels	Wellcome Trust (WELLCOTR)	106122/A/14/Z	Institute of Infection, Immunity & Inflammation
170547		The Wellcome Centre for Molecular Parasitology ( Core Support )	Andrew Waters	Wellcome Trust (WELLCOTR)	104111/Z/14/ZR	III - Parasitology