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

doi:10.1016/j.celrep.2017.10.044

Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes

Cell Rep. 2017 Nov 7;21(6):1624-1638. doi: 10.1016/j.celrep.2017.10.044.

Affiliations

¹ 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.
² Department of Immunology, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia.
³ Murdoch Children's Research Institute, The Royal Children's Hospital, Flemington Rd., Parkville, VIC 3052, Australia.
⁴ 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.
⁵ 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. Electronic address: [email protected].

PMID: 29117566
DOI: 10.1016/j.celrep.2017.10.044

Abstract

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.

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry
Adaptor Proteins, Signal Transducing / metabolism
Animals
B-Lymphocytes / cytology
B-Lymphocytes / immunology
B-Lymphocytes / metabolism
Cytokines / blood
Cytokines / metabolism
DEAD Box Protein 58 / metabolism
Down-Regulation / drug effects
Erythrocytes / immunology*
Humans
Immunity, Humoral / drug effects
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondrial Membrane Transport Proteins / metabolism
Mitochondrial Precursor Protein Import Complex Proteins
Poly I-C / pharmacology
RNA / immunology*
Sheep
Signal Transduction
Spleen / cytology
Spleen / drug effects
Spleen / metabolism
T-Lymphocytes / cytology
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
Toll-Like Receptors / metabolism

Substances

Adaptor Proteins, Signal Transducing
Cytokines
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Toll-Like Receptors
Tom70 protein, mouse
RNA
DEAD Box Protein 58
Poly I-C