J. Exp. Med., Volume 187, Number 1, January 5, 1998 1-14

Early Murine Cytomegalovirus (MCMV) Infection Induces Liver Natural Killer (NK) Cell Inflammation and Protection Through Macrophage Inflammatory Protein 1 (MIP-1)-dependent Pathways

By Thais P. Salazar-Mather, Jordan S. Orange, and Christine A. Biron

From the Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912

Natural killer (NK) cells mediate defense against early murine cytomegalovirus (MCMV) infections in liver. The chemokine, macrophage inflammatory protein 1 (MIP-1), can promote inflammatory responses. Our studies evaluated contributions of NK cells to early MCMV-induced liver inflammation and MIP-1 requirements for inflammation and delivery of antiviral defenses. NK cells were shown to be responsible for focal inflammation, and to be induced to migrate at high levels, in MCMV-infected livers. MIP-1 gene expression was elevated at coinciding times, and mice deficient in MIP-1 function were dramatically inhibited in both inflammatory and protective liver responses. The results precisely define MIP-1-dependent steps required to achieve NK cell inflammation during, and mechanisms promoting defense against, viral infections in tissues.

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