Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection

Jonathan M. Clingan, Kristin Ostrow, Karoline A. Hosiawa, Zhijian J. Chen, Mehrdad Matloubian

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. In this study, we demonstrate a nonredundant functional requirement for both nucleic acid-sensing TLRs and RIG-I-like receptors in the control of a mouse model of chronic viral infection. Whereas the RIG-I-like receptor pathway was important for production of type I IFNs and optimal CD8 + T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral Ab responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific Ab and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on Ab production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal Ab responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms.

Original languageEnglish (US)
Pages (from-to)4432-4440
Number of pages9
JournalJournal of Immunology
Volume188
Issue number9
DOIs
StatePublished - May 1 2012

Fingerprint

Virus Diseases
Nucleic Acids
Viruses
Infection
Adaptive Immunity
Immune System
Maintenance
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection. / Clingan, Jonathan M.; Ostrow, Kristin; Hosiawa, Karoline A.; Chen, Zhijian J.; Matloubian, Mehrdad.

In: Journal of Immunology, Vol. 188, No. 9, 01.05.2012, p. 4432-4440.

Research output: Contribution to journalArticle

Clingan, Jonathan M. ; Ostrow, Kristin ; Hosiawa, Karoline A. ; Chen, Zhijian J. ; Matloubian, Mehrdad. / Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection. In: Journal of Immunology. 2012 ; Vol. 188, No. 9. pp. 4432-4440.
@article{fa0462b96b2947c396cb588b35d82099,
title = "Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection",
abstract = "The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. In this study, we demonstrate a nonredundant functional requirement for both nucleic acid-sensing TLRs and RIG-I-like receptors in the control of a mouse model of chronic viral infection. Whereas the RIG-I-like receptor pathway was important for production of type I IFNs and optimal CD8 + T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral Ab responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific Ab and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on Ab production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal Ab responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms.",
author = "Clingan, {Jonathan M.} and Kristin Ostrow and Hosiawa, {Karoline A.} and Chen, {Zhijian J.} and Mehrdad Matloubian",
year = "2012",
month = "5",
day = "1",
doi = "10.4049/jimmunol.1103656",
language = "English (US)",
volume = "188",
pages = "4432--4440",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection

AU - Clingan, Jonathan M.

AU - Ostrow, Kristin

AU - Hosiawa, Karoline A.

AU - Chen, Zhijian J.

AU - Matloubian, Mehrdad

PY - 2012/5/1

Y1 - 2012/5/1

N2 - The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. In this study, we demonstrate a nonredundant functional requirement for both nucleic acid-sensing TLRs and RIG-I-like receptors in the control of a mouse model of chronic viral infection. Whereas the RIG-I-like receptor pathway was important for production of type I IFNs and optimal CD8 + T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral Ab responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific Ab and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on Ab production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal Ab responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms.

AB - The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. In this study, we demonstrate a nonredundant functional requirement for both nucleic acid-sensing TLRs and RIG-I-like receptors in the control of a mouse model of chronic viral infection. Whereas the RIG-I-like receptor pathway was important for production of type I IFNs and optimal CD8 + T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral Ab responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific Ab and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on Ab production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal Ab responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms.

UR - http://www.scopus.com/inward/record.url?scp=84860324628&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860324628&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1103656

DO - 10.4049/jimmunol.1103656

M3 - Article

C2 - 22447976

AN - SCOPUS:84860324628

VL - 188

SP - 4432

EP - 4440

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -