Calling in the troops: regulation of inflammatory cell trafficking through innate cytokine/chemokine networks.
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.
Departments of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA. Thais_Mather@brown.edu
Thais P
TP
Salazar-Mather
Kirsten L
KL
Hokeness
D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D006566:Herpesviridae Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000172:deficiency; D051379:Mice; D018448:Models, Immunological; D018146:Muromegalovirus / Q000276:immunology / Q000472:pathogenicity
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016207:Cytokines; D007370:Interferon Type I; D019402:Macrophage Inflammatory Proteins