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Cytosolic recognition of RNA drives the immune response to heterologous erythrocytes.


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

Type Journal
Authors Loetsch C, Warren J, Laskowski A, Vazquez-Lombardi R, Jandl C, Langley DB, Christ D, Thorburn DR, Ryugo DK, Sprent J, Batten M, King C.
Responsible Garvan Author A/Prof Cecile King
Publisher Name Cell Reports
Published Date 2017-11-07
Published Volume 21
Published Pages 162-1638
Status Published in-print
DOI 10.1016/j.celrep.2017.10.044