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.
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Renato
R
Barboza
Aramys Silva
AS
Reis
Leandro Gustavo
LG
da Silva
Lutero
L
Hasenkamp
Keitty Raquel Benevides
KR
Pereira
Niels Olsen Saraiva
NO
Câmara
Fabio Trindade Maranhão
FT
Costa
Maria Regina D'Império
MR
Lima
José Maria
JM
Alvarez
Silvia Beatriz
SB
Boscardin
Sabrina
S
Epiphanio
Cláudio Romero Farias
CR
Marinho
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D054884:Host-Pathogen Interactions; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D010920:Placenta / Q000276:immunology* / Q000469:parasitology; D010962:Plasmodium berghei / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000469:parasitology; D015398:Signal Transduction
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88