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Both TLR2 and TRIF contribute to interferon-β production during Listeria infection.

Aubry C, Corr SC, Wienerroither S, Goulard C, Jones R, Jamieson AM, Decker T, O'Neill LA, Dussurget O, Cossart P - PLoS ONE (2012)

Bottom Line: These pathways were stimulated to a lesser degree by wild-type L. monocytogenes.They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages.The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France.

ABSTRACT
Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.

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TLR3, but not TLR4, contributes to IFN-β response to Listeria in peritoneal macrophages.(A) PEM from WT C57BL/6J or tlr3−/− mice were infected with the parental EGDe strain (black bars), the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (n = 3). (B) PEM from WT C57BL/6J or tlr4−/− mice were infected with the parental EGDe strain (black bars), or the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (***, p<0.0001; n = 3).
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pone-0033299-g004: TLR3, but not TLR4, contributes to IFN-β response to Listeria in peritoneal macrophages.(A) PEM from WT C57BL/6J or tlr3−/− mice were infected with the parental EGDe strain (black bars), the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (n = 3). (B) PEM from WT C57BL/6J or tlr4−/− mice were infected with the parental EGDe strain (black bars), or the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (***, p<0.0001; n = 3).

Mentions: To examine the role of TLR3, which uses TRIF to trigger IFN-β synthesis, we compared induction of IFN-β in wild-type and tlr3−/− PEM infected with EGDe or ΔpgdA strains. IFN-β production was decreased in TLR3-deficient PEM infected with EGDe or ΔpgdA (Fig. 4A). We also compared induction of IFN-β in wild-type and tlr4−/− PEM infected with EGDe or ΔpgdA strains, as TLR4 can mediate TRIF-dependent synthesis of IFN-β. In contrast to TLR3-deficient PEM, TLR4-deficient PEM did not show a decrease in IFN-β response to EGDe or ΔpgdA (Fig. 4B). Thus, IFN-β induction in response to Listeria infection relies in part on TLR3 and does not require TLR4.


Both TLR2 and TRIF contribute to interferon-β production during Listeria infection.

Aubry C, Corr SC, Wienerroither S, Goulard C, Jones R, Jamieson AM, Decker T, O'Neill LA, Dussurget O, Cossart P - PLoS ONE (2012)

TLR3, but not TLR4, contributes to IFN-β response to Listeria in peritoneal macrophages.(A) PEM from WT C57BL/6J or tlr3−/− mice were infected with the parental EGDe strain (black bars), the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (n = 3). (B) PEM from WT C57BL/6J or tlr4−/− mice were infected with the parental EGDe strain (black bars), or the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (***, p<0.0001; n = 3).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3303824&req=5

pone-0033299-g004: TLR3, but not TLR4, contributes to IFN-β response to Listeria in peritoneal macrophages.(A) PEM from WT C57BL/6J or tlr3−/− mice were infected with the parental EGDe strain (black bars), the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (n = 3). (B) PEM from WT C57BL/6J or tlr4−/− mice were infected with the parental EGDe strain (black bars), or the ΔpgdA mutant (grey bars). After 7 h of infection, IFN-β levels were measured in supernatants by ELISA. Data are mean ± SD (***, p<0.0001; n = 3).
Mentions: To examine the role of TLR3, which uses TRIF to trigger IFN-β synthesis, we compared induction of IFN-β in wild-type and tlr3−/− PEM infected with EGDe or ΔpgdA strains. IFN-β production was decreased in TLR3-deficient PEM infected with EGDe or ΔpgdA (Fig. 4A). We also compared induction of IFN-β in wild-type and tlr4−/− PEM infected with EGDe or ΔpgdA strains, as TLR4 can mediate TRIF-dependent synthesis of IFN-β. In contrast to TLR3-deficient PEM, TLR4-deficient PEM did not show a decrease in IFN-β response to EGDe or ΔpgdA (Fig. 4B). Thus, IFN-β induction in response to Listeria infection relies in part on TLR3 and does not require TLR4.

Bottom Line: These pathways were stimulated to a lesser degree by wild-type L. monocytogenes.They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages.The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, France.

ABSTRACT
Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.

Show MeSH
Related in: MedlinePlus