Rat cytomegalovirus-encoded γ-chemokine vXCL1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells
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Rat cytomegalovirus-encoded γ-chemokine vXCL1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells. / Bauer, Agnieszka; Madela, Julia; Berg, Christian; Daugvilaite, Viktorija; Gurka, Stephanie; Mages, Hans Werner; Kroczek, Richard A.; Rosenkilde, Mette M.; Voigt, Sebastian.
In: Journal of Cell Science, Vol. 133, No. 5, jcs236190., 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rat cytomegalovirus-encoded γ-chemokine vXCL1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells
AU - Bauer, Agnieszka
AU - Madela, Julia
AU - Berg, Christian
AU - Daugvilaite, Viktorija
AU - Gurka, Stephanie
AU - Mages, Hans Werner
AU - Kroczek, Richard A.
AU - Rosenkilde, Mette M.
AU - Voigt, Sebastian
PY - 2020
Y1 - 2020
N2 - Dendritic cells (DCs) expressing the chemokine receptor XCR1 are specialized in antigen cross-presentation to control infections with intracellular pathogens. XCR1-positive (XCR1+) DCs are attracted by XCL1, a γ-chemokine secreted by activated CD8+ T cells and natural killer cells. Rat cytomegalovirus (RCMV) is the only virus known to encode a viral XCL1 analog (vXCL1) that competes for XCR1 binding with the endogenous chemokine. Here we show that vXCL1 from two different RCMV strains, as well as endogenous rat XCL1 (rXCL1) bind to and induce chemotaxis exclusively in rat XCR1+ DCs. Whereas rXCL1 activates the XCR1 Gi signaling pathway in rats and humans, both of the vXCL1s function as species-specific agonists for rat XCR1. In addition, we demonstrate constitutive internalization of XCR1 in XCR1-transfected HEK293A cells and in splenic XCR1+ DCs. This internalization was independent of β-arrestin 1 and 2 and was enhanced after binding of vXCL1 and rXCL1; however, vXCL1 appeared to be a stronger agonist. These findings suggest a decreased surface expression of XCR1 during DC cultivation at 37°C, and subsequent impairment of chemotactic activity and XCR1+ DC function.
AB - Dendritic cells (DCs) expressing the chemokine receptor XCR1 are specialized in antigen cross-presentation to control infections with intracellular pathogens. XCR1-positive (XCR1+) DCs are attracted by XCL1, a γ-chemokine secreted by activated CD8+ T cells and natural killer cells. Rat cytomegalovirus (RCMV) is the only virus known to encode a viral XCL1 analog (vXCL1) that competes for XCR1 binding with the endogenous chemokine. Here we show that vXCL1 from two different RCMV strains, as well as endogenous rat XCL1 (rXCL1) bind to and induce chemotaxis exclusively in rat XCR1+ DCs. Whereas rXCL1 activates the XCR1 Gi signaling pathway in rats and humans, both of the vXCL1s function as species-specific agonists for rat XCR1. In addition, we demonstrate constitutive internalization of XCR1 in XCR1-transfected HEK293A cells and in splenic XCR1+ DCs. This internalization was independent of β-arrestin 1 and 2 and was enhanced after binding of vXCL1 and rXCL1; however, vXCL1 appeared to be a stronger agonist. These findings suggest a decreased surface expression of XCR1 during DC cultivation at 37°C, and subsequent impairment of chemotactic activity and XCR1+ DC function.
KW - Chemokines
KW - Cytomegalovirus
KW - Dendritic cells
KW - G-protein-coupled receptor
KW - Immune evasion
KW - XCL1
KW - XCR1
U2 - 10.1242/jcs.236190
DO - 10.1242/jcs.236190
M3 - Journal article
C2 - 31649144
VL - 133
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 5
M1 - jcs236190.
ER -
ID: 235594533