Pulmonary paracoccidioidomycosis in AhR deficient hosts is severe and associated with defective Treg and Th22 responses
| Autor: | Eliseu Frank de Araújo, Nycolas W. Preite, Vera Lúcia Garcia Calich, Marc Veldhoen, Flávio V. Loures |
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| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Fungal infection Immunology lcsh:Medicine ANTIFÚNGICOS Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Basic Helix-Loop-Helix Transcription Factors Medicine Animals Indoleamine-Pyrrole 2 3 -Dioxygenase lcsh:Science Receptor Transcription factor Lung Mice Knockout Multidisciplinary business.industry Paracoccidioidomycosis lcsh:R Innate lymphoid cell Antagonist FOXP3 respiratory system medicine.disease Phenotype 3. Good health respiratory tract diseases Mice Inbred C57BL 030104 developmental biology Receptors Aryl Hydrocarbon 030220 oncology & carcinogenesis Th17 Cells Infectious diseases lcsh:Q business |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) |
| Popis: | © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. AhR is a ligand-activated transcription factor that plays an important role in the innate and adaptive immune responses. In infection models, it has been associated with host responses that promote or inhibit disease progression. In pulmonary paracoccidioidomycosis, a primary fungal infection endemic in Latin America, immune protection is mediated by Th1/Th17 cells and disease severity with predominant Th2/Th9/Treg responses. Because of its important role at epithelial barriers, we evaluate the role of AhR in the outcome of a pulmonary model of paracoccidioidomycosis. AhR-/- mice show increased fungal burdens, enhanced tissue pathology and mortality. During the infection, AhR-/- mice have more pulmonary myeloid cells with activated phenotype and reduced numbers expressing indoleamine 2,3 dioxygenase 1. AhR-deficient lungs have altered production of cytokines and reduced numbers of innate lymphoid cells (NK, ILC3 and NCR IL-22). The lungs of AhR-/- mice showed increased presence Th17 cells concomitant with reduced numbers of Th1, Th22 and Foxp3+ Treg cells. Furthermore, treatment of infected WT mice with an AhR-specific antagonist (CH223191) reproduced the main findings obtained in AhR-/- mice. Collectively our data demonstrate that in pulmonary paracoccidioidomycosis AhR controls fungal burden and excessive tissue inflammation and is a possible target for antifungal therapy. This work was supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-grant to VLGC 2011/51258-2 and 2016/23189-0; fellowship to EFA 2014/18668-2; grant to FVL 2018/14762-3; fellowship to NWP 2019-09278-8), European Union H2020 ERA project (No 667824 – EXCELLtoINNOV) to MV and Conselho Nacional de Pesquisas (CNPq). |
| Databáze: | OpenAIRE |
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