| Full text | |
| Author(s): |
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]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | PLoS Neglected Tropical Diseases; v. 7, n. 10 OCT 2013. |
| Web of Science Citations: | 14 |
| Abstract | |
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) | |
| FAPESP's process: | 04/14518-2 - Activation of immune system in pulmonary Paracoccidioidomycosis. Factors of fungus and of the host which influence the severity of the disease |
| Grantee: | Vera Lucia Garcia Calich |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 11/51258-2 - Influence of the enzyme indoleamine-2,3-dioxygenase (IDO) in the differentiation and function of dendritic cells and regulatory T cells in the pulmonary paracoccidioidomycosis of resistant and susceptible mice to P. brasiliensis infection |
| Grantee: | Vera Lucia Garcia Calich |
| Support Opportunities: | Regular Research Grants |