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Toll-like Receptors: Roles in Infection and Neuropathology pp 63–81Cite as

Toll-Like Receptors in CNS Viral Infections

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 336))

Abstract

Protection against viral infections is critically dependent upon the early production of significant levels of type 1 interferons and the expression of interferon-stimulated genes that function as the effectors of innate antiviral immunity. Activation of Toll-like receptors on cells of the immune system is known to play an important role in this process. In this chapter we review evidence for a role of TLRs in innate immune responses against viral infections of the central nervous system. By far the most extensive literature pertains to TLR3. Data from various laboratories have shown that TLR3 is expressed in cells endogenous to the CNS, particularly in astrocytes and microglia. Triggering TLR3 by synthetic dsRNA, poly I:C effectively induces innate antiviral responses as well as boosts adaptive immune responses. Additional experiments show cooperative responses between TLRs (3, 7/8 and 9) in mounting an effective antiviral immune response in the periphery. Perhaps the most exciting data are from patient populations that document the critical role that specific TLRs play in specific CNS infections. Studies also suggest that inappropriate activation of the TLRs can result in a pathogenic outcome rather than a protective one. Since TLR ligands are being actively considered for their antiviral and potential adjuvant effects, this will be an important issue to address in the context of the CNS environment.

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Abbreviations

(APOBEC3G):

Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G

(Cig5: viperin):

Cytomegalovirus-inducible gene 5

CNS:

Central nervous system

CpG ODN:

Unmethylated CpG oligodeoxynucleotide

dsRNA:

Double-stranded RNA

GM-CSF:

Granulocyte macrophage colony-stimulating factor

HAART:

Highly active antiretroviral therapy

HCMV:

Human cytomegalovirus

HIV:

Human immunodeficiency virus

IDO:

Indoleamine 2,3-dioxygenase

IFN:

Interferon

IKK:

IκB-activating kinase

IKKi:

Inducible IKK

IRF:

Interferon regulator factor

iNOS:

Inducible Nitric Oxide Synthase

IPS-1:

IFN-beta promoter stimulator 1

IRAK:

Interlukin-1 receptor-associated Kinase

ISG:

Interferon-stimulated gene

ISRE:

Interferon-stimulated response elemont

LPS:

Lipopolysaccharide

LRR:

Leucine-rich repeat

MAPK:

Mitogen-activated protein kinase

MCMV:

Murine cytomegalovirus

MDA-5:

Melanoma differentiation-associated gene 5

MS:

Multiple sclerosis

MyD88:

Myeloid differentiation factor 88

OAS:

2′,5′-Oligoadenylate synthase

PAMP:

Pathogen-associated molecular patterns

PCR:

Polymerase chain reaction

PKR:

dsRNA-dependent protein kinase

Poly I:C:

Polyinosinic:polycytidylic acid

RIG-I:

Retinoic acid-inducible gene I

RIP1:

Receptor-interacting protein 1

RLH:

RIG-I-like helicases

STAT1:

Signal transducer and activator 1

TANK:

TRAF family member-associated NF-κB activator-binding kinase 1

TBK1:

TANK-binding kinase 1

TIR:

Toll-like receptor IL-1 receptor domain

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor alpha

TRAF:

TNFα-receptor associated factor

TRIF:

TIR domain-containing adaptor-inducing IFNβ

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Acknowledgments

The authors and the work described in this chapter are in part supported by the PHS grants RO1 MH55477, Molecular Neuropathology Training Grant T32 NS007098, and the Einstein CFAR P30 AI051519, and NMSS RG3827A5. We thank Dr. Mark Rivieccio for his work described in this chapter. We also thank the Einstein Human Fetal Tissue Repository, the National NeuroAIDS Tissue Consortium (Manhattan HIV Brain Bank, Dr. Susan Morgello, director), and the NIH AIDS Research and Reference Reagent Program for tissues and reagents that were essential for generating data described in this chapter. We apologize to those whose relevant work could not be cited due to space limitations.

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  1. Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Hyeon-Sook Suh, Celia F. Brosnan & Sunhee C. Lee

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  1. Hyeon-Sook Suh
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  2. Celia F. Brosnan
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  3. Sunhee C. Lee
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Correspondence to Sunhee C. Lee .

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Editors and Affiliations

  1. Dept. Pathology & Microbiology, University of Nebraska Medical Center, S. 42nd St. 600 , Omaha, 68198-3135, U.S.A.

    Tammy Kielian

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Suh, HS., Brosnan, C.F., Lee, S.C. (2009). Toll-Like Receptors in CNS Viral Infections. In: Kielian, T. (eds) Toll-like Receptors: Roles in Infection and Neuropathology. Current Topics in Microbiology and Immunology, vol 336. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00549-7_4

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