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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

IFN-gamma-Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria

Texto completo
Autor(es):
da Silva, Henrique Borges [1] ; de Salles, Erika Machado [1] ; Panatieri, Raquel Hoffmann [2] ; Boscardin, Silvia Beatriz [2] ; Rodriguez-Malaga, Sergio Marcelo [1] ; Alvarez, Jose Maria [1] ; D'Imperio Lima, Maria Regina [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, BR-05508000 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF IMMUNOLOGY; v. 191, n. 10, p. 5160-5169, NOV 15 2013.
Citações Web of Science: 15
Resumo

The mechanism by which protective immunity to Plasmodium is lost in the absence of continued exposure to this parasite has yet to be fully elucidated. It has been recently shown that IFN-gamma produced during human and murine acute malaria primes the immune response to TLR agonists. In this study, we investigated whether IFN-gamma-induced priming is important to maintain long-term protective immunity against Plasmodium chabaudi AS malaria. On day 60 postinfection, C57BL/6 mice still had chronic parasitemia and efficiently controlled homologous and heterologous (AJ strain) challenge. The spleens of chronic mice showed augmented numbers of effector/effector memory (T-EM) CD4(+) cells, which is associated with increased levels of IFN-gamma-induced priming (i.e., high expression of IFN-inducible genes and TLR hyperresponsiveness). After parasite elimination, IFN-gamma-induced priming was no longer detected and protective immunity to heterologous challenge was mostly lost with >70% mortality. Spontaneously cured mice had high serum levels of parasite-specific IgG, but effector T/T-EM cell numbers, parasite-driven CD4(+) T cell proliferation, and IFN-gamma production were similar to noninfected controls. Remarkably, the priming of cured mice with low doses of IFN-gamma rescued TLR hyperresponsiveness and the capacity to control heterologous challenge, increasing the T-EM cell population and restoring the CD4(+) T cell responses to parasites. Contribution of TLR signaling to the CD4(+) T cell responses in chronic mice was supported by data obtained in mice lacking the MyD88 adaptor. These results indicate that IFN-gamma-induced priming is required to maintain protective immunity against P. chabaudi and aid in establishing the molecular basis of strain-transcending immunity in human malaria. (AU)

Processo FAPESP: 11/24038-1 - Efeitos da sinalização purinérgica na resposta imune e na patogenia durante a malária pelo Plasmodium chabaudi AS
Beneficiário:Maria Regina D'Império Lima
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/08559-1 - Caracterização dos mecanismos efetores da imunidade inata e adquirida no modelo de malária crônica em camundongos CD28KO infectados pelo Plasmodium chabaudi AS
Beneficiário:Henrique Borges da Silva
Linha de fomento: Bolsas no Brasil - Doutorado Direto