title: IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection.
abstract: Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells are assumed to be the major source of TNF and NO during Trypanosoma brucei brucei infection, their cellular origin remains unclear. In this study, we show that bone marrow-derived monocytes accumulate and differentiate to TNF/inducible NO synthase-producing dendritic cells (TIP-DCs) in the spleen, liver, and lymph nodes of T. brucei brucei-infected mice. Although TIP-DCs have been shown to play a beneficial role in the elimination of several intracellular pathogens, we report that TIP-DCs, as a major source of TNF and NO in inflamed organs, could contribute actively to tissue damage during the chronic stage of T. brucei brucei infection. In addition, the absence of IL-10 leads to enhanced differentiation of monocytes to TIP-DCs, resulting in exacerbated pathogenicity and early death of the host. Finally, we demonstrate that sustained production of IL-10 following IL-10 gene delivery treatment with an adeno-associated viral vector to chronically infected mice limits the differentiation of monocytes to TIP-DCs and protects the host from tissue damage.
authors.affiliation: Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
authors.forename: Kiavash
authors.initials: K
authors.lastname: Movahedi
authors.forename: Tom
authors.initials: T
authors.lastname: Bosschaerts
authors.forename: Thierry
authors.initials: T
authors.lastname: VandenDriessche
authors.forename: Marinee Khim
authors.initials: MK
authors.lastname: Chuah
authors.forename: Michel
authors.initials: M
authors.lastname: Hérin
authors.forename: Abel
authors.initials: A
authors.lastname: Acosta-Sanchez
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.forename: Muriel
authors.initials: M
authors.lastname: Moser
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
authors.forename: Lea
authors.initials: L
authors.lastname: Brys
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Alain
authors.initials: A
authors.lastname: Beschin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000229:Dependovirus / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D007111:Immunity, Cellular; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018512:Parasitemia / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D014346:Trypanosoma brucei brucei / Q000276:immunology* / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II