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Doctoral Thesis
DOI
10.11606/T.42.2017.tde-12042017-141823
Document
Author
Full name
Érika Machado de Salles
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Lima, Maria Regina D'Imperio (President)
Ferreira, Marcelo Urbano
Fonseca, Denise Morais da
Keller, Alexandre de Castro
Pontillo, Alessandra
Title in Portuguese
Efeitos da sinalização purinérgica durante a infecção aguda e crônica pelo Plasmodium chabaudi AS.
Keywords in Portuguese
Plasmodium chabaudi
ATP
Célula Tfh
Célula Th1
IFNγ
Receptor P2X7
Abstract in Portuguese
A malária permanece um sério problema de saúde em países subdesenvolvidos. O estágio sanguíneo da infecção é responsável por todos os sintomas associados com a malária. Recentemente, tem sido mostrado que receptores imunes inatos são capazes de detectar sinais de dano, tais como a adenosina trifosfato ATP. O receptor P2X7 detecta altas concentrações de ATP extracelular. Ao avaliarmos a parasitemia e os parâmetros clínicos da doença em camundongos C57BL/6 e P2X7-/-, observamos uma semelhança em ambos os grupos até o dia 7 p.i., mas após este período os camundongos P2X7-/- tiveram dificuldade de controlar a parasitemia e restaurar os parâmetros clínicos. O ineficiente controle da parasitemia durante o período agudo e crônico em camundongos P2X7-/- foi associado com a baixa produção de IFNγ. Além disso, o receptor P2X7 aumenta a expressão de T-bet em células Th1 e controla o número de células Tfh. Este estudo mostra que o equilíbrio mediado pelo receptor P2X7 entre os fatores de transcrição Bcl-6 e T-bet ajusta a imunidade celular e humoral na malária.
Title in English
Effects of purinergic signaling during acute and chronic infections by Plasmodium chabaudi AS.
Keywords in English
Plasmodium chabaudi
ATP
IFNγ
P2X7 receptor
Tfh cell
Th1 cell
Abstract in English
Malaria remains a serious healthcare problem in developing countries. The blood stage of infection is responsible for all symptoms associated with malaria. Recently, it has been shown that innate immune receptors are able to detect signals as adenosine triphosphate (ATP). P2X7 receptor detects high levels of extracellular ATP. Evaluating the parasitemia and clinical parameters in C57BL/6 (B6) and P2X7-/- mice, we observed a similarity in both groups to day 7 p.i., but after this period the P2X7-/- mice had difficulty in controlling the parasitemia and restoring the clinical parameters. The inefficient parasite control in acutely and chronically infected P2X7-/- mice was associated with low production of IFNγ. Furthermore, P2X7 receptor increases the expression of T-bet in Th1 cells and controls the Tfh cell number. This study provides a new insight into immunology by showing that the balance between T-bet and Bcl-6 transcriptional factors tunes the cellular and humoral immunity in malaria.
 
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Publishing Date
2017-04-12
 
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