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

• Published in: Nature communications 2018-10, Vol.9 (1), p.4516-16, Article 4516
• Main Authors: Rolot, Marion, Dougall, Annette M., Chetty, Alisha, Javaux, Justine, Chen, Ting, Xiao, Xue, Machiels, Bénédicte, Selkirk, Murray E., Maizels, Rick M., Hokke, Cornelis, Denis, Olivier, Brombacher, Frank, Vanderplasschen, Alain, Gillet, Laurent, Horsnell, William G. C., Dewals, Benjamin G.
• Format: Article
• Language: English
• Subjects: 14/1; 14/34; 14/5; 42/70; 49/31; 49/91; 631/250/1619/554/1834; 631/250/254; 631/250/255/1715; 631/250/255/2514; 64/60; Animals; Antigens; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell Line; Cricetinae; Herpesviridae Infections - immunology; Human health sciences; Humanities and Social Sciences; Immune system; Immunity; Immunologic Memory - immunology; Immunological memory; Immunologie & maladie infectieuse; Immunology; Immunology & infectious disease; Infections; Inflammation; Interleukin 4; Interleukin-4 - immunology; Life Sciences; Lungs; Lymphocytes; Lymphocytes T; Memory cells; Mice; multidisciplinary; Respiration; Respiratory Tract Infections - immunology; Rhadinovirus; Schistosoma mansoni; Schistosomiasis mansoni - immunology; Science; Science (multidisciplinary); Sciences de la santé humaine; Signaling; Tumor Virus Infections - immunology; Viral infections; Virtual memory systems
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06978-5

Infection with parasitic helminths can imprint the immune system to modulate bystander inflammatory processes. Bystander or virtual memory CD8 + T cells (T VM ) 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 T VM compartment. Here, we show that helminths expand CD44 hi CD62L hi CXCR3 hi CD49d lo T VM cells through direct IL-4 signaling in CD8 + T cells. Importantly, helminth-mediated conditioning of T VM 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. Parasitic helminth infection is known to impact upon the host response to other bystander inflammatory processes. Here the authors show that IL4 production induced by helminth infection results in expansion of bystander CD8+ memory T cells and enhanced control to viral infection.