Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Abstract

Alternatively activated macrophages (aaMφ) display molecular and biological characteristics that differ from those of classically activated macrophages (caMφ). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMφ, whereas in the late and chronic stages of infection, aaMφ develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMφ versus caMφ elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMφ as compared with caMφ. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-γ antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMφ and establish FIZZ1 and Ym1 as markers for aaMφ.