Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation.
Human rhinovirus (HRV)-induced respiratory infections are associated with elevated levels of IFN-gamma-inducible protein 10 (IP-10), which is an enhancer of T lymphocyte chemotaxis and correlates with symptom severity and T lymphocyte number. Increased IP-10 expression is exhibited by airway epithelial cells following ex vivo HRV challenge and requires intracellular viral replication; however, there are conflicting reports regarding the necessity of type I IFN receptor ligation for IP-10 expression. Furthermore, the involvement of resident airway immune cells, predominantly bronchoalveolar macrophages, in contributing to HRV-stimulated IP-10 elaboration remains unclear. In this regard, our findings demonstrate that ex vivo exposure of human peripheral blood monocytes and bronchoalveolar macrophages (monocytic cells) to native or replication-defective HRV serotype 16 (HRV16) resulted in similarly robust levels of IP-10 release, which occurred in a time- and dose-dependent manner. Furthermore, HRV16 induced a significant increase in type I IFN (IFN-alpha) release and STAT1 phosphorylation in monocytes. Neutralization of the type I IFN receptor and inhibition of JAK or p38 kinase activity strongly attenuated HRV16-stimulated STAT1 phosphorylation and IP-10 release. Thus, this work supports a model, wherein HRV16-induced IP-10 release by monocytic cells is modulated via autocrine/paracrine action of type I IFNs and subsequent JAK/STAT pathway activity. Our findings demonstrating robust activation of monocytic cells in response to native and/or replication-defective HRV16 challenge represent the first evidence indicating a mechanistic disparity in the activation of macrophages when compared with epithelial cells and suggest that macrophages likely contribute to cytokine elaboration following HRV challenge in vivo.
Korpi-Steiner
Nichole L
NL
Department of Biomolecular Chemistry, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706-0450, USA.
Bates
Mary Ellen
ME
Lee
Wai-Ming
WM
Hall
David J
DJ
Bertics
Paul J
PJ
D002450:Cell Communication / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D053612:Janus Kinases / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology*
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D053633:Receptor, Interferon alpha-beta; D053612:Janus Kinases