%0 Journal Article %1 10.1371/journal.ppat.1008279 %A Borst, K %A Flindt, S %A Blank, P %A Larsen, P K %A Chhatbar, C %A Skerra, J %A Spanier, J %A Hirche, C %A König, M %A Alanentalo, T %A Hafner, M %A Waibler, Z %A Pfeffer, K %A Sexl, V %A Sutter, G %A Müller, W %A Graalmann, T %A Kalinke, U %D 2020 %I Public Library of Science %J PLOS Pathog %K kalinke %N 2 %P 1-19 %T Selective reconstitution of IFN‑γ gene function in Ncr1+ NK cells is sufficient to control systemic vaccinia virus infection %U https://doi.org/10.1371/journal.ppat.1008279 %V 16 %X Author summary Viral infections induce interferon (IFN) responses that constitute a first line of defense. Type II IFN (IFN-γ) is required for protection against lethal vaccinia virus (VACV) infection. To address the cellular origin of protective IFN-γ responses during VACV infection, we generated IFN-γOFF mice, in which the endogenous IFN-γ gene function can be reconstituted in a Cre-dependent manner. IFN-γOFF mice were intercrossed with Ncr1-Cre mice that express Cre selectively in Ncr1+ innate cell subsests such as NK cells. Surprisingly, VACV infected IFN-γNcr1-ON mice mounted two waves of IFN-γ responses. Reconstitution of innate IFN-γ was sufficient to restore cytokine responses that supported normal myeloid cell distribution and survival upon VACV infection. In conclusion, IFN-γ derived from Ncr1+ innate immune cells is sufficient to elicit fully effective immune responses upon VACV infection. Our new mouse model is suitable to further address the role of Ncr1+ cell-derived IFN-γ also in other models of infection, as well as of autoimmunity and cancer.

@article{10.1371/journal.ppat.1008279, abstract = {Author summary Viral infections induce interferon (IFN) responses that constitute a first line of defense. Type II IFN (IFN-γ) is required for protection against lethal vaccinia virus (VACV) infection. To address the cellular origin of protective IFN-γ responses during VACV infection, we generated IFN-γOFF mice, in which the endogenous IFN-γ gene function can be reconstituted in a Cre-dependent manner. IFN-γOFF mice were intercrossed with Ncr1-Cre mice that express Cre selectively in Ncr1+ innate cell subsests such as NK cells. Surprisingly, VACV infected IFN-γNcr1-ON mice mounted two waves of IFN-γ responses. Reconstitution of innate IFN-γ was sufficient to restore cytokine responses that supported normal myeloid cell distribution and survival upon VACV infection. In conclusion, IFN-γ derived from Ncr1+ innate immune cells is sufficient to elicit fully effective immune responses upon VACV infection. Our new mouse model is suitable to further address the role of Ncr1+ cell-derived IFN-γ also in other models of infection, as well as of autoimmunity and cancer.}, added-at = {2020-02-06T11:18:09.000+0100}, author = {Borst, K and Flindt, S and Blank, P and Larsen, P K and Chhatbar, C and Skerra, J and Spanier, J and Hirche, C and König, M and Alanentalo, T and Hafner, M and Waibler, Z and Pfeffer, K and Sexl, V and Sutter, G and Müller, W and Graalmann, T and Kalinke, U}, biburl = {https://www.bibsonomy.org/bibtex/21ebedbe352351063f4464eabb8b98d4e/kalinke}, interhash = {b62c55c208592108fca6412b5581e1b0}, intrahash = {1ebedbe352351063f4464eabb8b98d4e}, journal = {PLOS Pathog}, keywords = {kalinke}, month = {02}, number = 2, pages = {1-19}, publisher = {Public Library of Science}, pubmedurl = {https://pubmed.ncbi.nlm.nih.gov/32023327-selective-reconstitution-of-ifn-gene-function-in-ncr1-nk-cells-is-sufficient-to-control-systemic-vaccinia-virus-infection/}, timestamp = {2020-02-06T11:18:09.000+0100}, title = {Selective reconstitution of IFN‑γ gene function in Ncr1+ NK cells is sufficient to control systemic vaccinia virus infection}, url = {https://doi.org/10.1371/journal.ppat.1008279}, volume = 16, year = 2020 }