Polarized monocyte response to cytokine stimulation

Dirk Nagorsen¹^,3 , Sara Deola¹ , Kina Smith¹ , Ena Wang¹ , Vladia Monsurro¹ , Paola Zanovello² , Francesco M Marincola¹ and Monica C Panelli¹

¹Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1502, USA

²Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, Padova 35100, Italy

³Current address: Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik III, Hindenburgdamm 30, 12200 Berlin, Germany

author email corresponding author email

Genome Biology 2005, 6:R15doi:10.1186/gb-2005-6-2-r15


Published:	21 January 2005

Subject areas: Immunology, Cell biology, Molecular biology, Genetics

Abstract

Background

Mononuclear phagocytes (MPs) stand at the crossroads between the induction of acute inflammation to recruit and activate immune effector cells and the downmodulation of the inflammatory process to contain collateral damage. This decision is extensively modulated by the cytokine microenvironment, which includes a broad array of cytokines whose direct effect on MPs remains largely unexplored. Therefore, we tested whether polarized responses of MPs to pathogens are related to the influence of selected cytokines or represent a mandatory molecular switch through which most cytokines operate.

Results

Circulating CD14⁺MPs were exposed to bacterial lipopolysaccharide (LPS) followed by exposure to an array of cytokines, chemokines and soluble factors involved in the immune response. Gene expression was studied by global transcript analysis. Two main classes of cytokines were identified that induced a classical or an alternative pathway of MP activation. Expression of genes affected by NFκB activation was most predictive of the two main classes, suggesting that this pathway is a fundamental target of cytokine regulation. As LPS itself induces a classical type of activation, the most dramatic modulation was observed toward the alternative pathway, suggesting that a broad array of cytokines may counteract the pro-inflammatory effects of bacterial components.

Conclusions

This analysis is directly informative of the primary effect of individual cytokines on the early stages of LPS stimulation and, therefore, may be most informative of the way MP maturation may be polarized at the early stages of the immune response.