Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes
Claudia Loetsch,
Joanna Warren,
Adrienne Laskowski,
Rodrigo Vazquez-Lombardi,
Christoph Jandl,
David B. Langley,
Daniel Christ,
David R. Thorburn,
David K. Ryugo,
Jonathan Sprent,
Marcel Batten,
Cecile King
Affiliations
Claudia Loetsch
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Joanna Warren
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia
Adrienne Laskowski
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Flemington Rd., Parkville, VIC 3052, Australia
Rodrigo Vazquez-Lombardi
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Christoph Jandl
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
David B. Langley
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Daniel Christ
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
David R. Thorburn
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Flemington Rd., Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville VIC 3010, Australia
David K. Ryugo
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Jonathan Sprent
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Marcel Batten
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
Cecile King
Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; St Vincent’s Clinical School, Department of Medicine, University of New South Wales, Sydney, NSW 2010, Australia; Corresponding author
Summary: The archetypal T cell-dependent antigen is sheep red blood cells (SRBCs), which have defined much of what we know about humoral immunity. Early studies using solubilized or sonicated SRBCs argued that the intact structure of SRBCs was important for optimal antibody responses. However, the reason for the requirement of intact SRBCs for the response to polyvalent protein antigen remained unknown. Here, we report that the immune response to SRBCs is driven by cytosolic recognition of SRBC RNA through the RIG-I-like receptor (RLR)-mitochondrial anti-viral signaling adaptor (MAVS) pathway. Following the uptake of SRBCs by antigen-presenting cells, the MAVS signaling complex governs the differentiation of both T follicular cells and antibody-producing B cells. Importantly, the involvement of the RLR-MAVS pathway precedes that of endosomal Toll-like receptor pathways, yet both are required for optimal effect. : Immunization with sheep red blood cells (SRBCs) has been used for almost a century to study antibody generation. Loetsch et al. now show that, after engulfment, SRBC RNA accesses antigen-presenting cell RNA-sensing pathways to stimulate the immune system.
