MyD88 signaling is directly involved in the development of murine placental Malaria

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-α) 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.

Programa Estratégico de Ciência, Tecnologia & Inovação nas Fundações Estaduais de Saúde (PECTI/AM Saúde), FAPEAM

São Paulo Research Foundation (FAPESP), 2009/53889-0

São Paulo Research Foundation (FAPESP), 2009/53256-7

São Paulo Research Foundation (FAPESP), 2011/17880-8

São Paulo Research Foundation (FAPESP), 2012/02270-2

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES, AUX-PE-PNPD 2751/2010

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES, AUX-PE-PNPD 258/2010

Conselho Nacional do Desenvolvimento Científico e Tecnológico - CNPq, 475771/2009-5

Conselho Nacional do Desenvolvimento Científico e Tecnológico - CNPq, 404213/2012