Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toll-like receptors (TLRs) recognize malaria parasites or their metabolites; however, their physiological roles in malaria infection in vivo are not fully understood. Here, we show that myeloid differentiation primary response gene 88 (MyD88)-dependent TLR signaling mediates brain pathogenesis of severe malaria infection, namely cerebral malaria (CM). A significant number of MyD88-, but not TIR domain containing adaptor-inducing IFN-beta (TRIF)-deficient or wild-type (WT) mice survived CM caused by Plasmodium berghei ANKA (PbA) infection. Although systemic parasitemia was comparable, sequestration of parasite and hemozoin load in the brain blood vessels was significantly lower in MyD88-deficient mice compared with those in TRIF-deficient or WT mice. Moreover, brain-specific pathological changes were associated with MyD88-dependent infiltration of CD8+, CCR5+ T cells and CD11c+ dendritic cells, including CD11c+, NK1.1+ and B220+ cells, and up-regulation of genes such as Granzyme B, Lipocalin 2, Ccl3 and Ccr5. Further studies using mice lacking various TLRs suggest that TLR2 and TLR9, but not TLR4, 5 and 7, were involved in CM. These results strongly suggest that TLR2- and/or TLR9-mediated, MyD88-dependent brain pathogenesis may play a critical role in CM, the lethal complication during PbA infection.
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PMID:Pathological role of Toll-like receptor signaling in cerebral malaria. 1713 46

Plasmodium parasites multiply within host erythrocytes, which contain high levels of iron, and parasite egress from these cells results in iron release and host anemia. Although Plasmodium requires host iron for replication, how host iron homeostasis and responses to these fluxes affect Plasmodium infection are incompletely understood. We determined that Lipocalin 2 (Lcn2), a host protein that sequesters iron, is abundantly secreted during human (P. vivax) and mouse (P. yoeliiNL) blood-stage malaria infections and is essential to control P. yoeliiNL parasitemia, anemia, and host survival. During infection, Lcn2 bolsters both host macrophage function and granulocyte recruitment and limits reticulocytosis, or the expansion of immature erythrocytes, which are the preferred target cell of P. yoeliiNL. Additionally, a chronic iron imbalance due to Lcn2 deficiency results in impaired adaptive immune responses against Plasmodium parasites. Thus, Lcn2 exerts antiparasitic effects by maintaining iron homeostasis and promoting innate and adaptive immune responses.
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PMID:Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria infection by reinforcing host iron metabolism. 2315 59

Malaria is a dangerous disease affecting millions around the globe. Biosynthesized nanoparticles are used against a variety of diseases including malaria worldwide. Here, silver nanoparticles (AgNPs) synthesized from the leaf extracts of Indigofera oblongifolia have been used in the treatment of mice infected with Plasmodium chabaudi to evaluate the expression of iron regulatory genes in the spleen. Infrared spectroscopy was used to identify the expected classes of compounds in the extract. AgNPs were able to decrease the parasitemia nearly similar to the used reference drug, chloroquine. In addition, AgNPs significantly decreased the spleen index after infection. Moreover, the iron distribution was increased after the treatment. Finally, AgNPs could regulate the mice spleen iron regulatory genes, Lipocalin 2 (Lcn2), transferrin receptor 1 (TFR1) and hepcidin antimicrobial peptide (Hamp). Taken together, our findings indicate that AgNPs have antimalarial activity and can control the state of iron in spleen. We need further investigations to determine mechanisms of action of the AgNPs.
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PMID:Biosynthesized silver nanoparticles regulate the iron status in the spleen of Plasmodium chabaudi-infected mice. 3265 98