Interferon Regulation of the Innate Response to Bacteria
Characterization of potent antiviral response to Interferons (IFNs) led to identification of the JAK-STAT signaling cascade almost two decades ago. More recently, studies have begun to explore how IFNs participate in the innate response to bacterial infec
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Abstract
Characterization of potent antiviral response to Interferons (IFNs) led to identification of the JAK-STAT signaling cascade almost two decades ago. More recently, studies have begun to explore how IFNs participate in the innate response to bacterial infections. This includes the activation of classic antibacterial responses, like expression on inducible nitric oxidase (iNOS) and GTPases, as well as the induction of autophagy. Not surprisingly, studies on its anti-bacterial activity of IFNs have provided important new insights into IFN biology and JAK-STAT signaling.
Introduction The potent antiviral activity of Interferons (IFNs) was first described by Isaacs and Lindenmann well over 50 years ago (Isaacs and Lindenmann 1957). Subsequent purification and cloning revealed that these four-helix bundle cytokines could be divided into two major groups, the type I and type II IFNs (reviewed in Uze et al. 2007). Type I IFNs (IFN-Is), the larger and more pleiotropic group included both fibroblast (a.k.a. – IFN-b) and leukocyte (a.k.a. – IFN-a’s) IFNs, whereas type II IFN was represented by a single member, immune IFN (a.k.a. – IFN-g). Consistent with these structural differences, type I and II IFNs were subsequently found to bind to distinct receptors and activate unique, but partially overlapping programs of
A. Abdul-Sater Department of Microbiology and Immunology, Columbia University, HHSC 1314, 701 West 168th Street, New York, NY 10032, USA C. Schindler (*) Departments of Microbiology & Immunology and Medicine, Columbia University, HHSC 1504, 701 West 168th Street, New York, NY 10032, USA e-mail: [email protected] Th. Decker and M. M€ uller (eds.), Jak-Stat Signaling: From Basics to Disease, DOI 10.1007/978-3-7091-0891-8_22, # Springer-Verlag Wien 2012
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signal transduction and gene expression (reviewed in Schindler and Plumlee 2008). A new family of type III IFNs (a.k.a. – IFN-ls or IL-28/29) was identified much more recently and found to bind a distinct epithelially expressed receptor (Kotenko et al. 2003; Sheppard et al. 2003). Although the antiviral activity mediated by each of these IFN classes was critical in their characterization, as well as their receptors and downstream signaling components, more recent studies have begun to explore the ability of IFNs to regulate both the innate response to bacteria and the subsequent transition to adaptive immunity (Douville and Hiscott 2010; Monroe et al. 2010; Trinchieri 2010). Intriguingly, in contrast to their essentially universal antiviral activity, the relationship between IFNs and an effective innate response to a bacterial infection is more complicated. In general, type II IFN has been found to potently activate the antibacterial program of phagocytes, especially towards bacteria that have evolved the capacity to replicate within cells (e.g. Chlamydiae, Fransciella tularensis, Mycobacterium tuberculosis, Listeria monocytogenes and Legionella pneumophila; (Monroe et al. 2010; Trinchieri 2010). Yet, the antibacter
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