Calling in the troops: regulation of inflammatory cell trafficking through innate cytokine/chemokine networks

Viral Immunol. 2003;16(3):291-306. doi: 10.1089/088282403322396109.


The recruitment of immune effector cells to localized sites of infection is crucial for the effective delivery of innate immune mechanisms. Under the conditions of infections with murine cytomegalovirus (MCMV), a herpesvirus with pathogenic potential, early immune functions are essential in the control of virus replication and virus-induced pathology. Our studies have demonstrated that the chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) is critical for natural killer (NK) cell inflammation and delivery of interferon (IFN)-gamma to mediate downstream protective responses against MCMV infection in liver. Moreover, IFN-alpha/beta-dependent mechanisms promote MIP-1alpha production and subsequently the accumulation of NK cells in liver. Taken together, the studies highlighted in this review define a unique in vivo pathway mediated by innate cytokines in regulating chemokine responses that are essential in the promotion of NK cell inflammation for localized antiviral defense. In addition, the downstream consequences of these events in enhancing endogenous adaptive immune responses will also be discussed. Overall, the innate cytokine/chemokine networks that are described emphasize the emerging importance of chemokine functions for protective immune responses during infection with viruses.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines / biosynthesis*
  • Cytokines / biosynthesis*
  • Herpesviridae Infections / immunology
  • Humans
  • Immunity, Innate
  • Inflammation / immunology*
  • Interferon Type I / biosynthesis
  • Killer Cells, Natural / immunology
  • Liver / immunology
  • Macrophage Inflammatory Proteins / biosynthesis
  • Macrophage Inflammatory Proteins / deficiency
  • Mice
  • Models, Immunological
  • Muromegalovirus / immunology
  • Muromegalovirus / pathogenicity


  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokines
  • Cytokines
  • Interferon Type I
  • Macrophage Inflammatory Proteins