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Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands.

Barbalat R, Lau L, Locksley RM, Barton GM - Nat. Immunol. (2009)

Bottom Line: The relevance of this recognition for antiviral immunity remains largely unexplained.TLR2-dependent induction of type I interferon occurred only in response to viral ligands, which indicates that TLR2 is able to discriminate between pathogen classes.Thus, the innate immune system can detect certain non-nucleic acid features of viruses and links this recognition to the induction of specific antiviral genes.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology and Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, California, USA.

ABSTRACT
Despite the paradigm that the innate immune system uses nucleic acid-specific receptors to detect viruses because of a lack of other conserved features, many viruses are recognized by Toll-like receptor 2 (TLR2) and TLR4. The relevance of this recognition for antiviral immunity remains largely unexplained. Here we report that TLR2 activation by viruses led to the production of type I interferon. TLR2-dependent induction of type I interferon occurred only in response to viral ligands, which indicates that TLR2 is able to discriminate between pathogen classes. We demonstrate that this specialized response was mediated by Ly6C(hi) inflammatory monocytes. Thus, the innate immune system can detect certain non-nucleic acid features of viruses and links this recognition to the induction of specific antiviral genes.

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A population of CD11b+CD11c- cells is responsible for TLR2-dependent type I IFN productiona) Bone marrow cells from C57BL/6 or TLR2-deficient mice were MACS sorted into CD11b-positive and CD11b-negative populations. The sorted cells were stimulated as indicated, and type I IFN was measured after 24 hours by bioassay. b) The same experiment was performed as described in (a), except that MACS sorting was based on CD11c. c) Splenocytes were harvested from CD11b-DTR transgenic mice 24 hours after injection with saline (PBS) or diptheria toxin. The resulting cells were stimulated as indicated and type I IFN production was measured after 24 hours by bioassay. All data are representative of at least 3 experiments.
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Figure 4: A population of CD11b+CD11c- cells is responsible for TLR2-dependent type I IFN productiona) Bone marrow cells from C57BL/6 or TLR2-deficient mice were MACS sorted into CD11b-positive and CD11b-negative populations. The sorted cells were stimulated as indicated, and type I IFN was measured after 24 hours by bioassay. b) The same experiment was performed as described in (a), except that MACS sorting was based on CD11c. c) Splenocytes were harvested from CD11b-DTR transgenic mice 24 hours after injection with saline (PBS) or diptheria toxin. The resulting cells were stimulated as indicated and type I IFN production was measured after 24 hours by bioassay. All data are representative of at least 3 experiments.

Mentions: We next sought to identify the population of cells in the bone marrow and spleen responsible for TLR2-dependent type I IFN induction. As an initial approach we used magnetic bead cell sorting to separate bone marrow cells based on expression of the common myeloid marker CD11b or the common DC marker CD11c. Strikingly, CD11b positively sorted cells were enriched for TLR2-dependent type I IFN production in response to vaccinia virus, while the CD11b negative cells no longer responded (Fig. 4a). In contrast, sorting based on CD11c did not alter the response (Fig. 4b). We obtained similar results with cells from transgenic mice expressing the diptheria toxin receptor (DTR) driven by the CD11b promoter (CD11b-DTR mice)28. Splenocytes harvested from CD11b-DTR mice injected with diptheria toxin no longer responded to vaccinia virus (Fig. 4c). These results suggest that a CD11b+CD11c- population of cells is responsible for TLR2-dependent type I IFN production.


Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands.

Barbalat R, Lau L, Locksley RM, Barton GM - Nat. Immunol. (2009)

A population of CD11b+CD11c- cells is responsible for TLR2-dependent type I IFN productiona) Bone marrow cells from C57BL/6 or TLR2-deficient mice were MACS sorted into CD11b-positive and CD11b-negative populations. The sorted cells were stimulated as indicated, and type I IFN was measured after 24 hours by bioassay. b) The same experiment was performed as described in (a), except that MACS sorting was based on CD11c. c) Splenocytes were harvested from CD11b-DTR transgenic mice 24 hours after injection with saline (PBS) or diptheria toxin. The resulting cells were stimulated as indicated and type I IFN production was measured after 24 hours by bioassay. All data are representative of at least 3 experiments.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 4: A population of CD11b+CD11c- cells is responsible for TLR2-dependent type I IFN productiona) Bone marrow cells from C57BL/6 or TLR2-deficient mice were MACS sorted into CD11b-positive and CD11b-negative populations. The sorted cells were stimulated as indicated, and type I IFN was measured after 24 hours by bioassay. b) The same experiment was performed as described in (a), except that MACS sorting was based on CD11c. c) Splenocytes were harvested from CD11b-DTR transgenic mice 24 hours after injection with saline (PBS) or diptheria toxin. The resulting cells were stimulated as indicated and type I IFN production was measured after 24 hours by bioassay. All data are representative of at least 3 experiments.
Mentions: We next sought to identify the population of cells in the bone marrow and spleen responsible for TLR2-dependent type I IFN induction. As an initial approach we used magnetic bead cell sorting to separate bone marrow cells based on expression of the common myeloid marker CD11b or the common DC marker CD11c. Strikingly, CD11b positively sorted cells were enriched for TLR2-dependent type I IFN production in response to vaccinia virus, while the CD11b negative cells no longer responded (Fig. 4a). In contrast, sorting based on CD11c did not alter the response (Fig. 4b). We obtained similar results with cells from transgenic mice expressing the diptheria toxin receptor (DTR) driven by the CD11b promoter (CD11b-DTR mice)28. Splenocytes harvested from CD11b-DTR mice injected with diptheria toxin no longer responded to vaccinia virus (Fig. 4c). These results suggest that a CD11b+CD11c- population of cells is responsible for TLR2-dependent type I IFN production.

Bottom Line: The relevance of this recognition for antiviral immunity remains largely unexplained.TLR2-dependent induction of type I interferon occurred only in response to viral ligands, which indicates that TLR2 is able to discriminate between pathogen classes.Thus, the innate immune system can detect certain non-nucleic acid features of viruses and links this recognition to the induction of specific antiviral genes.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology and Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, California, USA.

ABSTRACT
Despite the paradigm that the innate immune system uses nucleic acid-specific receptors to detect viruses because of a lack of other conserved features, many viruses are recognized by Toll-like receptor 2 (TLR2) and TLR4. The relevance of this recognition for antiviral immunity remains largely unexplained. Here we report that TLR2 activation by viruses led to the production of type I interferon. TLR2-dependent induction of type I interferon occurred only in response to viral ligands, which indicates that TLR2 is able to discriminate between pathogen classes. We demonstrate that this specialized response was mediated by Ly6C(hi) inflammatory monocytes. Thus, the innate immune system can detect certain non-nucleic acid features of viruses and links this recognition to the induction of specific antiviral genes.

Show MeSH
Related in: MedlinePlus