Interferon beta Expression is Attenuated In Human Model of Alternatively Activated Macrophages

Abstract

RATIONALE: Alternatively activated macrophages (M2) are induced by the Th2 cytokines and are implicated in hypersensitivity and allergy. An impediment to understanding the biology of human M2 cells is the lack of a reproducible in vitro human cell line model to improve upon the donor-to-donor variability of the primary cells. Using the human promonocytic cell line, THP1, we have successfully established a model to produce either classically activated macrophages (M1) or M2 cells. METHODS: THP1 cells were treated with PMA for 48 h followed by 96 h of 500 IU/ml IFN-g (THP-M1) or 100 IU/ml IL-4 (THP-M2). Both cell types were then treated with LPS for 4h and expression of IFN and inflammatory genes were measured by qRT- PCR. RESULTS: Compared to THP1-M1 cells, THP1-M2 cells exclusively express the scavenger-type mannose receptor (MRC1) and M2-related chemokines such as CCL-13, 17, 18 and 22. When treated with LPS, THP1-M2 cells were tolerant, expressing little or no TNF-alpha, CXCL-10 and 11. Furthermore, THP1-M2 expressed ∼100-fold less IFN-B and IFN-lambda1, and significantly lower levels of IFNAR1 and IFNAR2. CONCLUSION: This first description of human cell line model of alternatively activated macrophages demonstrates that the inflammatory response of M2 macrophages to LPS is impaired. Impaired expression of type I IFN and receptor subunits may explain poor respiratory viral clearance in allergic individuals.