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The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets.
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The present review discusses some of the new technologies that have been applied to elucidate how Plasmodium spp escape from the immune system and subvert the host physiology to orchestrate the regulation of its biological pathways. Our manuscript describes how techniques such as microarray approaches, RNA-Seq, and single-cell RNA sequencing have contributed to the discovery of transcripts and changed the concept of gene expression regulation in closely related malaria parasite species. Moreover, the text highlights the contributions of high-throughput RNA sequencing for the current knowledge of malaria parasite biology, physiology, vaccine target, and the revelation of new players in parasite signaling.
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Plasmodium , Transcriptoma , Biología , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Plasmodium/genética , Transcriptoma/genéticaRESUMEN
Neospora caninum is a protozoan parasite closely related to Toxoplasma gondii and has been studied for causing neuromuscular disease in dogs and abortions in cattle. It is recognized as one of the main transmissible causes of reproductive failure in cattle and consequent economic losses to the sector. In that sense, this study aimed to evaluate the role of Toll-like receptor 3 (TLR3)-TRIF-dependent resistance against N. caninum infection in mice. We observed that TLR3-/- and TRIF-/- mice presented higher parasite burdens, increased inflammatory lesions, and reduced production of interleukin 12p40 (IL-12p40), tumor necrosis factor (TNF), gamma interferon (IFN-γ), and nitric oxide (NO). Unlike those of T. gondii, N. caninum tachyzoites and RNA recruited TLR3 to the parasitophorous vacuole (PV) and translocated interferon response factor 3 (IRF3) to the nucleus. We also observed that N. caninum upregulated the expression of TRIF in murine macrophages, which in turn upregulated IFN-α and IFN-ß in the presence of the parasite. Furthermore, TRIF-/- infected macrophages produced lower levels of IL-12p40, while exogenous IFN-α replacement was able to completely restore the production of this key cytokine. Our results show that the TLR3-TRIF signaling pathway enhances resistance against N. caninum infection in mice, since it improves Th1 immune responses that result in controlled parasitism and reduced tissue inflammation, which are hallmarks of the disease.
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Proteínas Adaptadoras del Transporte Vesicular/inmunología , Coccidiosis/inmunología , Coccidiosis/parasitología , Neospora/fisiología , ARN Protozoario/inmunología , Receptor Toll-Like 3/inmunología , Proteínas Adaptadoras del Transporte Vesicular/genética , Animales , Coccidiosis/genética , Femenino , Interacciones Huésped-Parásitos , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Subunidad p40 de la Interleucina-12/genética , Subunidad p40 de la Interleucina-12/inmunología , Macrófagos/inmunología , Macrófagos/parasitología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neospora/genética , Neospora/inmunología , Óxido Nítrico/inmunología , ARN Protozoario/genética , Células TH1/inmunología , Células TH1/parasitología , Receptor Toll-Like 3/genéticaRESUMEN
Little is known about transcription factor regulation during the Plasmodium falciparum intraerythrocytic cycle. In order to elucidate the role of the P. falciparum (Pf)NF-YB transcription factor we searched for target genes in the entire genome. PfNF-YB mRNA is highly expressed in late trophozoite and schizont stages relative to the ring stage. In order to determine the candidate genes bound by PfNF-YB a ChIP-on-chip assay was carried out and 297 genes were identified. Ninety nine percent of PfNF-YB binding was to putative promoter regions of protein coding genes of which only 16% comprise proteins of known function. Interestingly, our data reveal that PfNF-YB binding is not exclusively to a canonical CCAAT box motif. PfNF-YB binds to genes coding for proteins implicated in a range of different biological functions, such as replication protein A large subunit (DNA replication), hypoxanthine phosphoribosyltransferase (nucleic acid metabolism) and multidrug resistance protein 2 (intracellular transport).
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Fixed bin frequencies for the VNTR loci D2S44, D4S139, D5S110, and D8S358 were determined in a Minas Gerais population sample. The data were generated by RFLP analysis of HaeIII-digested genomic DNA and chemiluminescent detection. The four VNTR loci have met Hardy-Weinberg equilibrium, and there was no association of alleles among VNTR loci. The frequency data can be used in forensic analyses and paternity tests to estimate the frequency of a DNA profile in the general Brazilian population