| Texto completo | |
| Autor(es): |
Felonato, Maira
[1]
;
Pina, Adriana
[1]
;
de Araujo, Eliseu Frank
[1]
;
Loures, Flavio V.
[1]
;
Bazan, Silvia B.
[1]
;
Feriotti, Claudia
[1]
;
Calich, Vera L. G.
[1]
Número total de Autores: 7
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil
Número total de Afiliações: 1
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PLoS One; v. 7, n. 11 NOV 30 2012. |
| Citações Web of Science: | 29 |
| Assunto(s): | Paracoccidioidomicose Células dendríticas Resposta imune |
| Resumo | |
Regulatory T (Treg) cells are fundamental in the control of immunity and excessive tissue pathology. In paracoccidioidomycosis, an endemic mycosis of Latin America, the immunoregulatory mechanisms that control the progressive and regressive forms of this infection are poorly known. Due to its modulatory activity on Treg cells, we investigated the effects of anti-CD25 treatment over the course of pulmonary infection in resistant (A/J) and susceptible (B10.A) mice infected with Paracoccidioides brasiliensis. We verified that the resistant A/J mice developed higher numbers and more potent Treg cells than susceptible B10.A mice. Compared to B10.A cells, the CD4(+)CD25(+)Foxp3(+) Treg cells of A/J mice expressed higher levels of CD25, CTLA4, GITR, Foxp3, LAP and intracellular IL-10 and TGF-beta. In both resistant and susceptible mice, anti-CD25 treatment decreased the CD4(+)CD25(+)Foxp3(+) Treg cell number, impaired indoleamine 2,3-dioxygenase expression and resulted in decreased fungal loads in the lungs, liver and spleen. In A/J mice, anti-CD25 treatment led to an early increase in T cell immunity, demonstrated by the augmented influx of activated CD4(+) and CD8(+) T cells, macrophages and dendritic cells to the lungs. At a later phase, the mild infection was associated with decreased inflammatory reactions and increased Th1/Th2/Th17 cytokine production. In B10.A mice, anti-CD25 treatment did not alter the inflammatory reactions but increased the fungicidal mechanisms and late secretion of Th1/Th2/Th17 cytokines. Importantly, in both mouse strains, the early depletion of CD25(+) cells resulted in less severe tissue pathology and abolished the enhanced mortality observed in susceptible mice. In conclusion, this study is the first to demonstrate that anti-CD25 treatment is beneficial to the progressive and regressive forms of paracoccidioidomycosis, potentially due to the anti-CD25-mediated reduction of Treg cells, as these cells have suppressive effects on the early T cell response in resistant mice and the clearance mechanisms of fungal cells in susceptible mice. (AU) | |
| Processo FAPESP: | 12/01765-8 - Caracterização das células t reguladoras na paracoccidioidomicose (pcm) pulmonar utilizando camundongos c57bl/6 transgênicos para a expressão de foxp3-gfp |
| Beneficiário: | Silvia Boschi Bazan |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |