title: Strong expression of TGF-beta in human host tissues around subcutaneous Dirofilaria repens.
abstract: Dirofilaria repens and other Dirofilaria species are widely distributed parasitic nematodes of carnivores, which occasionally are transmitted to men, causing subcutaneous nodules. In humans, it usually occurs only as single male or female filariae without production of microfilariae. The non-productive living or dead Dirofilaria worms in subcutaneous biopsies from 15 human patients permitted us to study the role of the pleiotropic and immunoregulatory cytokine transforming growth factor beta (TGF-beta) independent from the influence of microfilariae. Antiserum against latent TGF-beta 1 was used for an immunohistological examination. In the infiltrates around female and male filariae, there occurred strongly TGF-beta-positive macrophages, mast cells, endothelial cells, fibrocytes, and giant cells adjacent to dead worms. In one nodule, secondary lymph follicles were observed with clearly TGF-beta-positive B cells in the mantle zone and weakly positive macrophages and B cells in the germinal centre. A network of CD35-positive follicular dendritic cells was observed in the germinal centre. All Dirofilaria contained Wolbachia endobacteria, which probably had attracted the numerous TGF-beta-negative neutrophils near to the worm. Wolbachia were phagocytosed by neutrophils adjacent to dead filariae. Macrophages and lymphocytes expressed the MHC class II molecule HLA-DR in small accumulations of immune cells in the outer zone of the infiltrate and the mantle zone and germinal centre of secondary lymph follicles. It is concluded that single non-productive Dirofilaria worms elicit a strong expression of TGF-beta. This result is in accordance with observations on Onchocerca volvulus from patients with the hyporeactive (generalised) form.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359, Hamburg, Germany. nbrattig@bni-hamburg.de
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Brattig
authors.forename: Paul
authors.initials: P
authors.lastname: Racz
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Büttner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000378:metabolism; D004182:Dirofilaria / Q000276:immunology*; D004184:Dirofilariasis / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D012867:Skin / Q000469:parasitology; D040521:Subcutaneous Tissue / Q000469:parasitology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020577:Wolbachia / Q000472:pathogenicity
chemical_list: D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D016212:Transforming Growth Factor beta
references.citation: Tropenmed Parasitol. 1982 Mar;33(1):31-2
references.pmid: 7101439
references.citation: Adv Parasitol. 2008;66:193-285
references.pmid: 18486691
references.citation: Cell Res. 2009 Jan;19(1):116-27
references.pmid: 19114994
references.citation: Acta Trop. 2009 Nov;112(2):231-5
references.pmid: 19646411
references.citation: Annu Rev Cell Biol. 1990;6:597-641
references.pmid: 2177343
references.citation: J Leukoc Biol. 2009 Jan;85(1):29-33
references.pmid: 18818372
references.citation: Parasitol Res. 1996;82(2):117-24
references.pmid: 8825205
references.citation: Science. 1987 Jan 23;235(4787):442-7
references.pmid: 2432664
references.citation: Parasitology. 2002 Nov;125(Pt 5):431-44
references.pmid: 12458827
references.citation: Circ Res. 2005 Sep 16;97(6):512-23
references.pmid: 16166562
references.citation: Microbes Infect. 2010 Jul;12(7):555-64
references.pmid: 20359544
references.citation: Microbes Infect. 2008 Mar;10(3):313-24
references.pmid: 18339571
references.citation: Curr Microbiol. 2000 Aug;41(2):96-100
references.pmid: 10856373
references.citation: Infect Immun. 2000 Nov;68(11):6402-10
references.pmid: 11035752
references.citation: J Parasitol. 2008 Dec;94(6):1421-3
references.pmid: 19127968
references.citation: Parasitol Res. 2010 Aug;107(3):657-66
references.pmid: 20524133
references.citation: Microbes Infect. 2001 May;3(6):439-46
references.pmid: 11377205
references.citation: Immunol Cell Biol. 2008 Jan;86(1):92-7
references.pmid: 17768418
references.citation: Microbes Infect. 2003 Apr;5(4):261-73
references.pmid: 12706439
references.citation: Trends Parasitol. 2009 Sep;25(9):404-9
references.pmid: 19720566
references.citation: Parasite Immunol. 2005 Oct-Nov;27(10-11):417-29
references.pmid: 16179035
references.citation: Southeast Asian J Trop Med Public Health. 1999 Jun;30(2):375-8
references.pmid: 10774712
references.citation: Vet Parasitol. 2008 Dec 10;158(3):223-31
references.pmid: 18922634
references.citation: Parasitol Res. 2009 Nov;105(6):1531-8
references.pmid: 19784672
references.citation: Trop Med Parasitol. 1988 Dec;39 Suppl 4:390-417
references.pmid: 2852393
references.citation: Microbes Infect. 2004 Jan;6(1):113-28
references.pmid: 14738900
references.citation: Annu Rev Immunol. 2006;24:99-146
references.pmid: 16551245
references.citation: Parasitol Res. 2009 Sep;105(3):731-41
references.pmid: 19452170