title: Functional and phenotypic characteristics of alternative activation induced in human monocytes by interleukin-4 or the parasitic nematode Brugia malayi.
abstract: Human monocytes from patients with patent filarial infections are studded with filarial antigen and express markers associated with alternative activation of macrophages (MΦ). To explore the role of filaria-derived parasite antigen in differentiation of human monocytes, cells were exposed to microfilariae (mf) of Brugia malayi, and their phenotypic and functional characteristics were compared with those of monocytes exposed to factors known to generate either alternatively (interleukin-4 [IL-4]) or classically (macrophage colony-stimulating factor [MCSF]) activated MΦ. IL-4 upregulated mRNA expression of CCL13, CCL15, CCL17, CCL18, CCL22, CLEC10A, MRC1, CADH1, CD274, and CD273 associated with alternative activation of MΦ but not arginase 1. IL-4-cultured monocytes had a diminished ability to promote proliferation of both CD4(+) and CD8(+) T cells compared to that of unexposed monocytes. Similar to results with IL-4, exposure of monocytes to live mf induced upregulation of CCL15, CCL17, CCL18, CCL22, CD274, and CD273 and downregulation of Toll-like receptor 3 (TLR3), TLR5, and TLR7. In contrast to results with MCSF-cultured monocytes, exposure of monocytes to mf resulted in significant inhibition of the phagocytic ability of these cells to the same degree as that seen with IL-4. Our data suggest that short exposure of human monocytes to IL-4 induces a phenotypic characteristic of alternative activation and that secreted filarial products skew monocytes similarly.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. rsemnani@niaid.nih.gov
authors.forename: Roshanak Tolouei
authors.initials: RT
authors.lastname: Semnani
authors.forename: Lily
authors.initials: L
authors.lastname: Mahapatra
authors.forename: Vanessa
authors.initials: V
authors.lastname: Moore
authors.forename: Vivornpun
authors.initials: V
authors.lastname: Sanprasert
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005368:Filariasis / Q000276:immunology / Q000469:parasitology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008842:Microfilariae / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010641:Phenotype; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D051193:Toll-Like Receptors; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor