In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology

• Grant number: 13/20623-2
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: November 01, 2013
• End date: April 30, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vera Lucia Garcia Calich
• Grantee: Vera Lucia Garcia Calich
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Backgroung: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM) the most important systemic mycosis in Latin America. Th1 immunity and IFN-³ 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-³, TNF-±, nitric oxide (NO) and MCP-1. For in vivo studies, IL-10-/- and WT mice were i.t. infected with 1 x 106 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)