Human Cytomegalovirus Activates Inflammatory Cytokine Responses via CD14 and Toll-Like Receptor 2

Author:

Compton Teresa1,Kurt-Jones Evelyn A.2,Boehme Karl W.1,Belko John2,Latz Eicke2,Golenbock Douglas T.2,Finberg Robert W.2

Affiliation:

1. McArdle Laboratory for Cancer Research, University of Wisconsin—Madison Medical School, Madison, Wisconsin 53706

2. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Abstract

ABSTRACT Human cytomegalovirus (CMV) is a ubiquitous opportunistic pathogen that causes significant morbidity and mortality in immuncompromised people. An understanding of how CMV induces and circumvents host immunity is of critical importance in efforts to design effective therapeutics. It was recently discovered that mere cell contact by CMV particles leads to profound modulation of cellular gene expression, including induction of inflammatory cytokines and interferon-stimulated genes characteristic of innate immune detection. These findings suggest that a membrane receptor recognizes a CMV envelope protein(s), leading to innate immune activation. Here, we show that the pattern recognition receptors Toll-like receptor 2 (TLR2) and CD14 recognize CMV virions and trigger inflammatory cytokine production. Induction of inflammatory cytokines is mediated via TLR2-dependent activation of NF-κB. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory cytokines, identification of the host membrane detection machinery may ultimately lead to improved therapeutics.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference66 articles.

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