IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection
| Autor: | Guilliams, M., Movahedi, K., Bosschaerts, Tom, VandenDriessche, Thierry, Chuah, Marinee, Michel, Herin, Acosta-Sanchez, Abel, Ma, L., Moser, M., Van Ginderachter, J.a. |
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| Přispěvatelé: | Division of Gene Therapy & Regenerative Medicine, Cell Biology and Histology |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
mice
Nitric Oxide/antagonists & inhibitors Trypanosomiasis African/enzymology Nitric Oxide Synthase Type II/biosynthesis Genetic Vectors/immunology Parasitemia/enzymology Tumor Necrosis Factor-alpha/biosynthesis Cell Differentiation/immunology Immunophenotyping Cell Line Tumor Necrosis Factor-alpha/antagonists & inhibito Monocytes/metabolism parasitic diseases Trypanosomiasis African/immunology Interleukin-10/deficiency Interleukin-10/genetics Mice Knockout Immunity Cellular Mice Inbred BALB C Interleukin-10/physiology Nitric Oxide Synthase Type II/antagonists & inhibi Monocytes/pathology Monocytes/enzymology Nitric Oxide/biosynthesis Parasitemia/pathology Monocytes/immunology Dendritic Cells/enzymology Trypanosoma brucei brucei/pathogenicity Mice Inbred C57BL Parasitemia/immunology Trypanosoma brucei brucei/immunology Interleukin-10/administration & dosage Trypanosomiasis African/pathology Trypanosomiasis African/prevention & contro Genetic Vectors/administration & dosage Parasitemia/prevention & control |
| 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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