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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.)

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

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Autor(es):
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Barboza, Renato [1, 2] ; Reis, Aramys Silva [1] ; da Silva, Leandro Gustavo [1] ; Hasenkamp, Lutero [1] ; Benevides Pereira, Keitty Raquel [1] ; Saraiva Camara, Niels Olsen [3] ; Maranhao Costa, Fabio Trindade [4] ; D'Imperio Lima, Maria Regina [3] ; Alvarez, Jose Maria [3] ; Boscardin, Silvia Beatriz [1] ; Epiphanio, Sabrina [5] ; Farias Marinho, Claudio Romero [1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema - Brazil
[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil
[4] Univ Estadual Campinas, Inst Biol, Dept Genet Evolucao & Bioagentes, Campinas, SP - Brazil
[5] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Biol, Diadema - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Infection and Immunity; v. 82, n. 2, p. 830-838, FEB 2014.
Citações Web of Science: 8
Resumo

Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88(-/-) and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88(-/-) mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions. (AU)

Processo FAPESP: 09/53889-0 - Estudo dos mecanismos imunopatológicos envolvidos na malária durante a gravidez
Beneficiário:Cláudio Romero Farias Marinho
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 09/53256-7 - Identificação e caracterização da síndrome respiratória aguda murina associada à malária severa: estudo da interação parasito-hospedeiro
Beneficiário:Sabrina Epiphanio
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 11/17880-8 - Os receptores do tipo Toll (TLR) e NOD (NLR) na patogênese da malária associada à gravidez: efeitos e mecanismos
Beneficiário:Renato Barboza
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
Beneficiário:Niels Olsen Saraiva Câmara
Linha de fomento: Auxílio à Pesquisa - Temático