Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling

Franz Puttur; Marcela Francozo; Gülhas Solmaz; Carlos Bueno; Marc Lindenberg; Melanie Gohmert; Maxine Swallow; Dejene Tufa; Roland Jacobs; Stefan Lienenklaus; Anja A. Kühl; Lisa Borkner; Luka Cicin-Sain; Bernard Holzmann; Hermann Wagner; Luciana Berod; Tim Sparwasser

doi:10.1016/j.celrep.2016.09.055

Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling

Franz Puttur, Marcela Francozo, Gülhas Solmaz, Carlos Bueno, Marc Lindenberg, Melanie Gohmert, Maxine Swallow, Dejene Tufa, Roland Jacobs, Stefan Lienenklaus, Anja A. Kühl, Lisa Borkner, Luka Cicin-Sain, Bernard Holzmann, Hermann Wagner, Luciana Berod, Tim Sparwasser

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Abstract

Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c⁺ dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid DCs (pDCs), conventional DCs (cDCs) promote robust NK cell effector function and MCMV clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates NK cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of TLR9 and MyD88 signaling in individual DC subsets and evaluate the mechanism by which cDCs control MCMV immunity.

Original language	English (US)
Pages (from-to)	1113-1127
Number of pages	15
Journal	Cell reports
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2016.09.055
State	Published - Oct 18 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2016 The Authors

Keywords

MCMV
NK cells
TLR9-MyD88 signaling
conventional DC
plasmacytoid DC

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2016.09.055

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Puttur, F., Francozo, M., Solmaz, G., Bueno, C., Lindenberg, M., Gohmert, M., Swallow, M., Tufa, D., Jacobs, R., Lienenklaus, S., Kühl, A. A., Borkner, L., Cicin-Sain, L., Holzmann, B., Wagner, H., Berod, L., & Sparwasser, T. (2016). Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling. Cell reports, 17(4), 1113-1127. https://doi.org/10.1016/j.celrep.2016.09.055

Puttur, F, Francozo, M, Solmaz, G, Bueno, C, Lindenberg, M, Gohmert, M, Swallow, M, Tufa, D, Jacobs, R, Lienenklaus, S, Kühl, AA, Borkner, L, Cicin-Sain, L, Holzmann, B, Wagner, H, Berod, L & Sparwasser, T 2016, 'Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling', Cell reports, vol. 17, no. 4, pp. 1113-1127. https://doi.org/10.1016/j.celrep.2016.09.055

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abstract = "Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid DCs (pDCs), conventional DCs (cDCs) promote robust NK cell effector function and MCMV clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates NK cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of TLR9 and MyD88 signaling in individual DC subsets and evaluate the mechanism by which cDCs control MCMV immunity.",

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T1 - Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling

AU - Puttur, Franz

AU - Francozo, Marcela

AU - Solmaz, Gülhas

AU - Bueno, Carlos

AU - Lindenberg, Marc

AU - Gohmert, Melanie

AU - Swallow, Maxine

AU - Tufa, Dejene

AU - Jacobs, Roland

AU - Lienenklaus, Stefan

AU - Kühl, Anja A.

AU - Borkner, Lisa

AU - Cicin-Sain, Luka

AU - Holzmann, Bernard

AU - Wagner, Hermann

AU - Berod, Luciana

AU - Sparwasser, Tim

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Y1 - 2016/10/18

N2 - Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid DCs (pDCs), conventional DCs (cDCs) promote robust NK cell effector function and MCMV clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates NK cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of TLR9 and MyD88 signaling in individual DC subsets and evaluate the mechanism by which cDCs control MCMV immunity.

AB - Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c+ dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production. In addition, we show that in the absence of plasmacytoid DCs (pDCs), conventional DCs (cDCs) promote robust NK cell effector function and MCMV clearance in a TLR9/MyD88-dependent manner. Simultaneously, cDC-derived IL-15 regulates NK cell degranulation by TLR9/MyD88-independent mechanisms. Overall, we compartmentalize the cellular contribution of TLR9 and MyD88 signaling in individual DC subsets and evaluate the mechanism by which cDCs control MCMV immunity.

KW - MCMV

KW - NK cells

KW - TLR9-MyD88 signaling

KW - conventional DC

KW - plasmacytoid DC

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Conventional Dendritic Cells Confer Protection against Mouse Cytomegalovirus Infection via TLR9 and MyD88 Signaling

Abstract

Bibliographical note

Keywords

UN SDGs

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