Modulation of human macrophage activity by Ascaris antigens is dependent on macrophage polarization state

Parasitic worms (helminths) are known to actively modulate host immune responses and inflammation. The aim of this study was to investigate if adult body fluid (ABF) from the helminth Ascaris suum has immunomodulatory effects on different subtypes of human monocyte-derived macrophages (Mɸ) in vitro. Mɸs were exposed to A. suum ABF at different stages of their differentiation and/or polarization. Mɸ were first differentiated from monocytes into either uncommitted (M-), classically activated (M(GM-CSF)) or alternatively activated (M(M-CSF)) phenotypes and then stimulated with lipopolysaccharide (LPS). ABF strongly suppressed LPS-induced TNF-α, IL-6 and IL-10 secretion in M(GM-CSF)s, however in M(M-CSF)s only TNF-α was suppressed, with these cells secreting high levels of IL-10 which was not affected by ABF treatment. To determine if ABF modulated the differentiation of previously uncommitted Mɸ to either type 1 or type 2 Mɸ, monocytes were differentiated with human serum into (M-)s and then polarized by IFN-γ/LPS or IL-4 treatment in the presence of ABF. Under these conditions, ABF did not modulate cytokine secretion but did reduce CD80 expression in IFNγ/LPS-polarized cells but not IL-4-polarized cells. Finally, we demonstrate that when monocytes are differentiated into M(GMCSF)s in the presence of ABF, subsequent inflammatory responses are markedly suppressed. Our data suggest that ABF inhibits cytokine secretion and co-stimulatory molecule expression in classically activated Mɸ but not in alternatively activated Mɸ, indicating selective action of ABF depending on Mɸ subtype. Moreover, ABF appears to exert stronger activity when acting upon Mɸ that have already been polarized to the type 1 phenotype, rather than influencing the polarization process per se.