IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection
| Autor: | Alain Beschin, Muriel Moser, Patrick De Baetselier, Tom Bosschaerts, Martin Guilliams, Marinee Khim Chuah, Michel Hérin, Thierry VandenDriessche, Abel Acosta-Sanchez, Lea Brys, Jo A. Van Ginderachter, Ling Ma, Kiavash Movahedi |
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| Přispěvatelé: | Cellular and Molecular Immunology, Basic (bio-) Medical Sciences, Division of Gene Therapy & Regenerative Medicine |
| Rok vydání: | 2009 |
| Předmět: |
Nitric Oxide/antagonists & inhibitors
Nitric Oxide Synthase Type II/biosynthesis Genetic Vectors/immunology Parasitemia/enzymology Nitric Oxide Synthase Type II Parasitemia Monocytes Cell Differentiation/immunology Tumor Necrosis Factor-alpha/antagonists & inhibito Monocytes/metabolism Immunology and Allergy Trypanosomiasis African/immunology Mice Knockout Immunity Cellular Mice Inbred BALB C Nitric Oxide Synthase Type II/antagonists & inhibi biology Monocytes/pathology Monocytes/enzymology Parasitemia/pathology Cell Differentiation Dendritic Cells/enzymology Dependovirus Interleukin-10 Parasitemia/immunology Trypanosoma brucei brucei/immunology Interleukin 10 medicine.anatomical_structure Genetic Vectors/administration & dosage Parasitemia/prevention & control Female Tumor necrosis factor alpha mice Trypanosomiasis African/enzymology Genetic Vectors Trypanosoma brucei brucei Immunology Tumor Necrosis Factor-alpha/biosynthesis Spleen Trypanosoma brucei Gene delivery Nitric Oxide Immunophenotyping Cell Line parasitic diseases medicine Animals Interleukin-10/deficiency Interleukin-10/genetics Interleukin-10/physiology Tumor Necrosis Factor-alpha Nitric Oxide/biosynthesis Intracellular parasite Monocytes/immunology Dendritic Cells Dendritic cell biology.organism_classification Trypanosoma brucei brucei/pathogenicity Mice Inbred C57BL Trypanosomiasis African Cell culture Interleukin-10/administration & dosage Trypanosomiasis African/pathology Trypanosomiasis African/prevention & contro |
| Zdroj: | Vrije Universiteit Brussel |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.2.1107 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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