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Master's Dissertation
DOI
10.11606/D.42.2009.tde-02022010-124420
Document
Author
Full name
Eliseu Frank de Araujo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Calich, Vera Lucia Garcia (President)
Giannini, Maria José Soares Mendes
Negro, Sonia Jancar
Title in Portuguese
A IDO controla a carga fúngica e a imunidade celular de camundongos suscetíveis e resistentes à infecção pelo Paracoccidioides brasiliensis.
Keywords in Portuguese
1-Metil triptofano
3 dioxigenase
Citocinas
Indolamina 2
Linfócitos
Macrófagos
Paracoccidioidomicose
Abstract in Portuguese
Indolamina-2,3-dioxigenase (IDO) e o catabolismo do triptofano estão envolvidos no controle da imunidade inata e adaptativa contra patógenos. Investigamos o papel da IDO na paracoccidiodomicose pulmonar (PCM) de animais suscetíveis (B10.A) e resistentes (A/J) ao fungo. Observou-se uma ação marcante da IDO ao início da doença de camundongos B10.A onde a enzima controla a carga fúngica mas, também, induz anergia de células TCD4+ e TCD8+, creditada em parte à expansão de células Treg e aumento de linfócitos em apoptose. Em camundongos A/J, a IDO controla a carga fúngica inicial, porém, o seu efeito supressor sobre linfócitos TCD4+ é somente observado na 8ª semana. Assim como em camundongos B10.A, a IDO mostrou-se indutora de células Treg e linfócitos em apoptose durante a imunidade desenvolvida por camundongos A/J. Em conclusão, foi demonstrado pela primeira vez que a IDO exerce um importante mecanismo microbicida e imunorregulador na PCM de hospedeiros resistentes e suscetíveis ao P. brasiliensis.
Title in English
IDO controls the fungal loads and cellular immunity in pulmonary paracoccidiodomycosis developed by susceptible and resistant mice to the fungus.
Keywords in English
1-Methyl tryptophan
3 dioxygenase
Cytokines
Indoleamine 2
Lymphocytes
Macrophages
Paracoccidioidomycosis
Abstract in English
Indoleamine-2, 3-dioxygenase (IDO) and tryptophan catabolism are involved in the control of innate and adaptive immunity against pathogens. We investigated the role of IDO in the pulmonary paracoccidiodomycosis developed by susceptible (B10.A) and resistant (A/J) mice to the fungus. We verified that IDO plays a different effect in innate the immunity of B10.A and A/J mice. Early in the infection, IDO controlled the fungal loads but also induced anergy of CD4+ and CD8+ T cells of B10.A mice. T cell anergy was partially due to the expansion of Treg cells and increased apoptosis of lymphocytes. In resistant mice, IDO controlled the initial fungal loads, but exerted a suppressive effect on T lymphocytes only at week 8. As in B10.A mice IDO was shown to induce Treg cells and apoptosis of lymphocytes in the course of immune response developed by resistant mice. In conclusion our work showed for the first time that IDO play an important role in the fungicidal and immunoregulatory mechanisms developed by susceptible and resistant mice to P. brasiliensis infection.
 
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Publishing Date
2010-03-04
 
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