Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Diverse cellular responses to external cues are controlled by a small number of signal-transduction pathways, but how the specificity of functional outcomes is achieved remains unclear. Here we describe a mechanism for signal integration based on the functional coupling of two distinct signaling pathways widely used in leukocytes: the ITAM pathway and the Jak-STAT pathway. Through the use of the receptor for interferon-γ (IFN-γR) and the ITAM adaptor Fcγ as an example, we found that IFN-γ modified responses of the phagocytic antibody receptor FcγRI (CD64) to specify cell-autonomous antimicrobial functions. Unexpectedly, we also found that in peritoneal macrophages, IFN-γR itself required tonic signaling from Fcγ through the kinase PI(3)K for the induction of a subset of IFN-γ-specific antimicrobial functions. Our findings may be generalizable to other ITAM and Jak-STAT signaling pathways and may help explain signal integration by those pathways.

Original publication

DOI

10.1038/ni.2845

Type

Journal article

Journal

Nat Immunol

Publication Date

04/2014

Volume

15

Pages

333 - 342

Keywords

Animals, Bacterial Load, Cells, Cultured, Immunoglobulin Fc Fragments, Immunoreceptor Tyrosine-Based Activation Motif, Interferon-gamma, Janus Kinase 2, Listeriosis, Macrophages, Mice, Mice, Inbred Strains, Mice, Knockout, Nitric Oxide Synthase Type II, Phagocytosis, Phosphoinositide-3 Kinase Inhibitors, Protein Engineering, Receptor Cross-Talk, Receptors, IgG, Receptors, Interferon, STAT1 Transcription Factor, Signal Transduction, Transcriptional Activation, Interferon gamma Receptor