| First Author | Lee SH | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 8 | Pages | 4223-34 |
| PubMed ID | 24048899 | Mgi Jnum | J:206257 |
| Mgi Id | MGI:5548272 | Doi | 10.4049/jimmunol.1300910 |
| Citation | Lee SH, et al. (2013) Identifying the initiating events of anti-Listeria responses using mice with conditional loss of IFN-gamma receptor subunit 1 (IFNGR1). J Immunol 191(8):4223-34 |
| abstractText | Although IFN-gamma is required for resolution of Listeria monocytogenes infection, the identities of the IFN-gamma-responsive cells that initiate the process remain unclear. We addressed this question using novel mice with conditional loss of IFN-gammaR (IFNGR1). Itgax-cre(+)Ifngr1(f/f) mice with selective IFN-gamma unresponsiveness in CD8alpha(+) dendritic cells displayed increased susceptibility to infection. This phenotype was due to the inability of IFN-gamma-unresponsive CD8alpha(+) dendritic cells to produce the initial burst of IL-12 induced by IFN-gamma from TNF-alpha-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-gamma-driven cascade involving CD8alpha(+) dendritic cells and NK/NKT cells induces the rapid production of IL-12 that initiates the anti-Listeria response. |
