title: Over expression of IL-10 by macrophages overcomes resistance to murine filariasis.
abstract: Individuals infected with parasitic helminths are able to tolerate the presence of parasites for considerable time without clinical pathology. Immunosuppressive responses induced by the filarial parasite are considered responsible for this long-lasting relationship, inuring to the benefit of both parasite and host. In order to directly link IL-10 with parasite survival, we infected mice, in which over expression of IL-10 was restricted to macrophages under control of the CD68 promoter (macIL-10tg), with Litomosoides sigmodontis. IL-10 overexpression by macrophages led to increased susceptibility with a significantly higher number of adult worms. Most profound, IL-10 overexpression was sufficient to convert resistant FVB wild-type mice towards a patent phenotype, since microfilariae were exclusively found in macIL-10tg mice. These findings were associated with reduced Th2 cytokine production in macIL-10tg mice. Expression of arginase-1, Ym1 and Fizz1, genes that are found strongly expressed in murine alternatively activated macrophages, were detected in macIL-10tg mice. Thus, IL-10 produced by macrophages with characteristics of alternative activation can overcome resistance and allow full patency in murine filariasis.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-St. 25, 53105 Bonn, Germany. specht@microbiology-bonn.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Marieke A
authors.initials: MA
authors.lastname: Hoeve
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allen
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D060467:Disease Resistance / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005368:Filariasis / Q000276:immunology*; D005370:Filarioidea / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D016205:Sigmodontinae; D013047:Specific Pathogen-Free Organisms
chemical_list: D016207:Cytokines; D016753:Interleukin-10