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

J Leukoc Biol. 2006 Dec;80(6):1364-74. doi: 10.1189/jlb.0606412. Epub 2006 Oct 4.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Communication / immunology
  • Chemokine CXCL10
  • Chemokines, CXC / immunology*
  • Chemokines, CXC / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / immunology
  • Humans
  • Interferon Type I / immunology
  • Interferon Type I / metabolism
  • Janus Kinases / immunology
  • Janus Kinases / metabolism
  • Macrophage Activation / immunology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / virology
  • Phosphorylation
  • Protein Processing, Post-Translational / immunology
  • Receptor, Interferon alpha-beta / biosynthesis
  • Receptor, Interferon alpha-beta / immunology*
  • Rhinovirus / immunology*
  • STAT1 Transcription Factor / immunology*
  • STAT1 Transcription Factor / metabolism
  • Virus Replication / immunology*


  • CXCL10 protein, human
  • Chemokine CXCL10
  • Chemokines, CXC
  • Interferon Type I
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Receptor, Interferon alpha-beta
  • Janus Kinases