Novel Markers for Alternative Activation of Macrophages: Macrophage Galactose‐Type C‐Type Lectins 1 and 2

Van Den Bergh, R.; Hassanzadeh, G. H.; Brys, L.; Dahal, B. K.; Brandt, J.; Grooten, J.; Brombacher, F.; Vanham, G.; Noël, W.; Bogaert, P.; Boonefaes, T.; Kindt, A.; De Baetselier, P.; Raes, G.

In parallel with the Th1/Th2 dichotomy, macrophages are capable of developing into functionally and molecularly distinct subpopulations, due to differences in, for example cytokine environment and pathological conditions. While the best‐studied, classically activated macrophage is induced by type I stimuli such as IFN‐γ, a type II cytokine environment antagonizes the classical activation of macrophages and is capable of alternatively activating macrophages. However, molecular markers associated with these type II cytokine‐dependent, alternatively activated macrophages remain scarce. Besides the earlier documented markers macrophage mannose receptor and arginase 1, we recently demonstrated that murine alternatively activated macrophages are characterized by increased expression of FIZZ1 and Ym. We now report that expression of the two members of the mouse macrophage galactose‐type C‐type lectin gene family, termed mMGL1 and mMGL2, is induced in diverse populations of alternatively activated macrophages, including peritoneal macrophages elicited during infection with the protozoan Trypanosoma brucei or the Helminth Taenia crassiceps, and alveolar macrophages elicited in a mouse model of allergic asthma. We also demonstrate that, in vitro, interleukin‐4 and interleukin‐13 upregulate mMGL1 and mMGL2 expression and that, in vivo, induction of mMGL1 and mMGL2 is dependent on interleukin‐4 receptor signalling. Moreover, we show that regulation of MGL expression is similar in human monocytes and monocyte‐derived macrophages. Hence, macrophage galactose‐type C‐type lectins represent novel markers for both murine and human alternatively activated macrophages; thus, paving the way for further characterization of the phenotype of macrophages occurring in Th2 conditions.