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 Kay Ryugo, Jonathan Sprent, Marcel Batten, Cecile King

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)1624-1638
Number of pages15
JournalCell Reports
Volume21
Issue number6
DOIs
StatePublished - Nov 7 2017
Externally publishedYes

Fingerprint

Sheep
Blood
Erythrocytes
Cells
Antigen-Presenting Cells
RNA
Antibodies
Immunization
immune RNA
Antigens
Antibody-Producing Cells
T-cells
Immune system
Toll-Like Receptors
Humoral Immunity
Antibody Formation
Immune System
B-Lymphocytes
T-Lymphocytes
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Loetsch, C., Warren, J., Laskowski, A., Vazquez-Lombardi, R., Jandl, C., Langley, D. B., ... King, C. (2017). Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes. Cell Reports, 21(6), 1624-1638. https://doi.org/10.1016/j.celrep.2017.10.044

Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes. / Loetsch, Claudia; Warren, Joanna; Laskowski, Adrienne; Vazquez-Lombardi, Rodrigo; Jandl, Christoph; Langley, David B.; Christ, Daniel; Thorburn, David R.; Ryugo, David Kay; Sprent, Jonathan; Batten, Marcel; King, Cecile.

In: Cell Reports, Vol. 21, No. 6, 07.11.2017, p. 1624-1638.

Research output: Contribution to journalArticle

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 2017, 'Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes', Cell Reports, vol. 21, no. 6, pp. 1624-1638. https://doi.org/10.1016/j.celrep.2017.10.044
Loetsch C, Warren J, Laskowski A, Vazquez-Lombardi R, Jandl C, Langley DB et al. Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes. Cell Reports. 2017 Nov 7;21(6):1624-1638. https://doi.org/10.1016/j.celrep.2017.10.044
Loetsch, Claudia ; Warren, Joanna ; Laskowski, Adrienne ; Vazquez-Lombardi, Rodrigo ; Jandl, Christoph ; Langley, David B. ; Christ, Daniel ; Thorburn, David R. ; Ryugo, David Kay ; Sprent, Jonathan ; Batten, Marcel ; King, Cecile. / Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes. In: Cell Reports. 2017 ; Vol. 21, No. 6. pp. 1624-1638.
@article{a49eb2312273432480a3bf02aa60e6be,
title = "Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes",
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. 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.",
author = "Claudia Loetsch and Joanna Warren and Adrienne Laskowski and Rodrigo Vazquez-Lombardi and Christoph Jandl and Langley, {David B.} and Daniel Christ and Thorburn, {David R.} and Ryugo, {David Kay} and Jonathan Sprent and Marcel Batten and Cecile King",
year = "2017",
month = "11",
day = "7",
doi = "10.1016/j.celrep.2017.10.044",
language = "English (US)",
volume = "21",
pages = "1624--1638",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes

AU - Loetsch, Claudia

AU - Warren, Joanna

AU - Laskowski, Adrienne

AU - Vazquez-Lombardi, Rodrigo

AU - Jandl, Christoph

AU - Langley, David B.

AU - Christ, Daniel

AU - Thorburn, David R.

AU - Ryugo, David Kay

AU - Sprent, Jonathan

AU - Batten, Marcel

AU - King, Cecile

PY - 2017/11/7

Y1 - 2017/11/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85034111547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034111547&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.10.044

DO - 10.1016/j.celrep.2017.10.044

M3 - Article

C2 - 29117566

AN - SCOPUS:85034111547

VL - 21

SP - 1624

EP - 1638

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -