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.
%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
}