In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology

Autor(es)

Costa, Tania A. ^[1] ; Bazan, Silvia B. ^[1] ; Feriotti, Claudia ^[1] ; Araujo, Eliseu F. ^[1] ; Bassi, Enio J. ^[1] ; Loures, Flavio V. ^[1] ; Calich, Vera L. G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 7, n. 10 OCT 2013.
• Citações Web of Science: 14

Resumo

Background: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. Th1 immunity and IFN-gamma activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. Methodology/Principal Findings: Wild type (WT) and IL-10(-/-) C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb) infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/-) mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-gamma, TNF-alpha, nitric oxide (NO) and MCP-1. For in vivo studies, IL-10(-/-) and WT mice were i.t. infected with 1x10(6) Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/-) mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/-) mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+) and CD8(+) T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/-) mice. Conclusions/Significance: Our work demonstrates for the first time that IL-10 plays a detrimental effect to pulmonary PCM due to its suppressive effect on the innate and adaptive immunity resulting in progressive infection and precocious mortality of infected hosts. (AU)

• Processo FAPESP: 10/52275-5 - Influência dos receptores de imunidade inata (TLR2, TLR4 e Dectina-1) no comportamento de células dendríticas e na determinação do padrão de imunidade adaptativa dos hospedeiros contra o paracocciodióides
• Beneficiário: Vera Lucia Garcia Calich
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/14518-2 - Ativação do sistema imune na Paracoccidioidomicose pulmonar. Fatores do fungo e do hospedeiro que influenciam na gravidade da doença
• Beneficiário: Vera Lucia Garcia Calich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/51258-2 - Influência da enzima indolamina-2,3-dioxigenase (IDO) na diferenciação e função das células dendríticas e T reguladoras na paracoccidiodomicose pulmonar de camundongos resistentes e suscetíveis ao P. brasiliensis
• Beneficiário: Vera Lucia Garcia Calich
• Modalidade de apoio: Auxílio à Pesquisa - Regular