Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system

Netea, Mihai G.; Graaf, Chantal A. A. van der; Meer, J.W.M. van der; Kullberg, Bart Jan

doi:10.1189/jlb.1103543

Cited by 253 publications

(185 citation statements)

References 84 publications

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“…In TLR3 Ϫ/Ϫ mice, viral growth was unaffected but lung pathology was more severe, an effect linked to an increase in Th2-type responses in the TLR3 Ϫ/Ϫ mice, thus reflecting a role for TLR3 in promoting Th1-type immune responses. A similar role for TLR has been noted following activation of dendritic cells (29).…”

Section: Discussionsupporting

confidence: 62%

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

Rivieccio¹,

Suh²,

Zhao³

et al. 2006

The Journal of Immunology

129

128

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TLR3 functions as a viral nucleic acid sentinel activated by dsRNA viruses and virus replication intermediates within intracellular vesicles. To explore the spectrum of genes induced in human astrocytes by TLR3, we used a microarray approach and the analog polyriboinosinic polyribocytidylic acid (pIC) as ligand. As expected for TLR activation, pIC induced a wide array of cytokines and chemokines known for their role in inflammatory responses, as well as up-regulation of the receptor itself. The data also showed activation of a broad spectrum of antiviral response genes. To determine whether pIC induced an antiviral state in astrocytes, a pseudotyped HIV viral particle, vesicular stomatitis virus g-env-HIV-1, was used. pIC significantly abrogated HIV-1 replication, whereas IL-1, which also potently activates astrocytes, did not. One of the most highly up-regulated genes on microarray was the protein viperin/cig5. We found that viperin/cig5 expression was dependent on IFN regulatory factor 3 and NF-κB signaling, and that repetitive stimulation with pIC, but not IL-1, further increased expression. Viperin induction could also be substantially inhibited by neutralizing Abs to IFN-β, as could HIV-1 replication. To explore a role for viperin in IFN-β-mediated inhibition of HIV-1, we used an RNA interference (RNAi) approach. RNAi directed against viperin, but not a scrambled RNAi, significantly inhibited viperin expression, and also significantly reversed pIC-induced inhibition of HIV-1 replication. We conclude that viperin contributes to the antiviral state induced by TLR3 ligation in astrocytes, supporting a role for astrocytes as part of the innate immune response against infection in the CNS.

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Section: Discussionsupporting

confidence: 62%

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

Rivieccio¹,

Suh²,

Zhao³

et al. 2006

The Journal of Immunology

129

128

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“…IFN-␥ production by DCs has been detected in response to intracellular pathogens and certain cytokines (24,25,27). The early (IFN-␥ and TNF-␣) and later, more-potent (IL-12 p70, IFN-␥, and TNF-␣) responses induced by poly(I:C) might contribute to the more effective DC maturation (7,36,46,62), resulting in efficient inhibition of infection. A recent report highlighted that poly(I:C) was able to boost mucosal HIV-specific CD4 T-cell responses in mice when antigen was targeted to DCs by Abs specific to CD205 (69).…”

Section: Discussionmentioning

confidence: 99%

Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

Trapp

Derby

Singer

et al. 2009

J Virol

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“…DCs express several pattern-recognition receptors (PRRs) that specifically recognize distinct PAMPs displayed on fungal surfaces including C-type lectin receptors (CLRs) (21) and Tolllike receptors (TLRs) (22). The macrophage mannose receptor (MMR), member of the CLR family, has been shown to recognize C. albicans on DCs (23), and we previously demonstrated that the DC-associated CLR DC-SIGN (CD209) is also involved in binding and internalization of C. albicans by human DCs (24).…”

mentioning

confidence: 99%

Dendritic Cell Interaction with Candida albicans Critically Depends on N-Linked Mannan

Cambi

Netea

Mora-Montes

et al. 2008

Journal of Biological Chemistry

Self Cite

212

200

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The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, because a detailed characterization at the structural level is lacking. Antigen-presenting dendritic cells (DCs), strategically located at mucosal surfaces and in the skin, may play an important role in anti-Candida protective immunity. However, the contribution of the various Candida-associated molecular patterns and their counter-receptors to DC function remains unknown. Here, we demonstrate that two C-type lectins, DC-SIGN and the macrophage mannose receptor, specifically mediate C. albicans binding and internalization by human DCs. Moreover, by combining a range of C. albicans glycosylation mutants with receptor-specific blocking and cytokine production assays, we determined that N-linked mannan but not O-linked or phosphomannan is the fungal carbohydrate structure specifically recognized by both C-type lectins on human DCs and directly influences the production of the proinflammatory cytokine IL-6. Better insight in the carbohydrate recognition profile of C-type lectins will ultimately provide relevant information for the development of new drugs targeting specific fungal cell wall antigens.

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Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system

Cited by 253 publications

References 84 publications

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

Dendritic Cell Interaction with Candida albicans Critically Depends on N-Linked Mannan

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