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Identifying the initiating events of anti-Listeria responses using mice with conditional loss of IFN-? receptor subunit 1 (IFNGR1).


ABSTRACT: Although IFN-? is required for resolution of Listeria monocytogenes infection, the identities of the IFN-?-responsive cells that initiate the process remain unclear. We addressed this question using novel mice with conditional loss of IFN-?R (IFNGR1). Itgax-cre(+)Ifngr1(f/f) mice with selective IFN-? unresponsiveness in CD8?(+) dendritic cells displayed increased susceptibility to infection. This phenotype was due to the inability of IFN-?-unresponsive CD8?(+) dendritic cells to produce the initial burst of IL-12 induced by IFN-? from TNF-?-activated NK/NKT cells. The defect in early IL-12 production resulted in increased IL-4 production that established a myeloid cell environment favoring Listeria growth. Neutralization of IL-4 restored Listeria resistance in Itgax-cre(+)Ifngr1(f/f) mice. We also found that Itgax-cre(+)Ifngr1(f/f) mice survived infection with low-dose Listeria as the result of a second wave of IL-12 produced by Ly6C(hi) monocytes. Thus, an IFN-?-driven cascade involving CD8?(+) dendritic cells and NK/NKT cells induces the rapid production of IL-12 that initiates the anti-Listeria response.

PROVIDER: S-EPMC3874833 | BioStudies |

REPOSITORIES: biostudies

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