E-MTAB-4791
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-4791 | ExpressionAtlas | 2016-06-06
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:The aim of the present study was to analyze the effect of protective vaccination on the transcriptome of the liver towards the end of the crisis phase in vaccination-induced self-healing infections of Plasmodium chabaudi in comparison to lethal infections in non-protected Balb/c mice using Agilentâs gene expression microarrays.
2016-10-01 | E-MTAB-4791 | biostudies-arrayexpress
Project description:Malaria, caused by Plasmodium parasites is responsible for the illness of millions of individuals each year. Plasmodium sporozoites inoculated by mosquitoes migrate to the liver and infect hepatocytes prior to release of merozoites that initiate symptomatic blood-stage malaria. Parasites are thought to be restricted to hepatocytes throughout this obligate liver-stage of replication and differentiation. In contrast to this notion, we found that a subset of hepatic dendritic CD11c+ cells co-expressing F4/80, CD103, CD207 and CSF1R, acquired a substantial parasite burden during the liver-stage of malaria, but only after initial hepatocyte infection. These CD11c+ cells found in the infected liver and liver-draining lymph nodes exhibited transcriptionally and phenotypically enhanced antigen-presentation functions; and primed protective CD8 T cell responses against Plasmodium liver-stage restricted antigens. Our findings uncover a novel aspect of Plasmodium biology as well as the fundamental mechanism by which CD8 T cell responses are primed against liver-stage malaria.
2019-02-05 | GSE126110 | GEO
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. In response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10935 | biostudies-arrayexpress
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. I response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10939 | biostudies-arrayexpress
Project description:Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and -140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria.
2022-08-11 | PXD033964 | Pride
Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. Vaccinees received 3 doses of 1.8 X 106 irradiated sporozoites. Efficacy was measured by challenged by controlled human malaria infections (CHMI), and against naturally occurring Pf Infections in Malian adults during the malaria transmission season
2022-08-20 | GSE211599 | GEO
Project description:Severe presentations of malaria emerge as parasites from Plasmodium spp. proliferate and lyse red blood cells (RBC), producing extracellular hemoglobin (HB). The heme prosthetic groups are released upon HB oxidation generating circulating labile heme. Here we asked whether scavenging of extracellular HB and/or labile heme, by haptoglobin (HP) and/or hemopexin (HPX), respectively, is protective against severe presentations of malaria. We found that circulating labile heme is an independent risk factor for cerebral and non-cerebral severe presentations of P. falciparum malaria. Labile heme was negatively correlated with HP and HPX, which were however, not risk factors for severe P. falciparum malaria. Genetic HP and/or HPX deletion in mice led to accumulation of labile heme in plasma and kidneys in response to Plasmodium (chabaudi chabaudi) infection. This was associated with increased mortality and acute kidney injury (AKI) in ageing but not adult mice, corroborated in P. falciparum malaria by a an inverse correlation between HPX and heme with serological markers of AKI. In conclusion, HP and HPX exert an age-dependent protective effect against malaria that counters the pathogenesis of AKI in mice and presumably in humans.
2024-01-30 | GSE253390 | GEO
Project description:Cerebral Malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. Currently, our understanding of the factors that trigger progression of malaria to CM is limited. Here, by infecting experimental CM (ECM) resistant (Balb/c) and ECM susceptible (C57BL/6) mice with ECM causing (ANKA) and non-ECM causing (NK65) Plasmodium berghei (Pb) parasite strains, we revealed that in resistant host, infection by ECM causing parasite develops similar to infection by non-ECM causing parasite in susceptible host in terms of parasite growth in host, disease course and host immune response against parasite. Our comparative gene expression analysis revealed that in Balb/c host, gene expression of Pb ANKA parasite is remarkably different from, the gene expression of Pb ANKA in C57BL/6 but similar to the gene expression of non-ECM causing Pb NK65 in C57BL/6. Thus, host has a critical influence on parasite behavior which ultimately determines the course of malaria disease.
2023-02-21 | GSE215359 | GEO
Project description:The aim of the present study was to analyze the effect of protective vaccination on the miRNome of the liver during the crisis phase in vaccination-induced self-healing infections of Plasmodium chabaudi in comparison to lethal infections in non-protected Balb/c mice using Agilentâs microRNA expression microarrays.
2017-04-01 | E-MTAB-5301 | biostudies-arrayexpress
Project description:Malaria is by far the world’s most significant tropical infectious disease and over the last a few decades large-scale malaria epidemics have happened in almost all continents. Plasmodium falciparum and Plasmodium vivax account for over 90% of the total malaria cases worldwide. The estimated number of annual clinical cases of vivax malaria is even higher than that of falciparum malaria, but yet the morbidity associated with this infection and its spectrum of disease is largely neglected. Identification of serum/plasma proteins, which exhibit altered abundance at the onset and during the acute phase of any infection, could be informative to understand the pathobiology of different infectious diseases and host responses against the invading pathogens. To this end, in recent years, quite a few research groups including us have investigated alterations in serum/plasma proteome in severe and non-severe falciparum malaria (and also vivax malaria) to study malaria pathogenesis. In all these studies, serum/plasma proteome of the malaria patients have been analyzed during the febrile stages of the infection, either at the onset of the disease or at the fastigium stage. However, temporal profiling of serum/plasma proteome during acute and remission stages in malaria, which can provide snapshots of the transient and enduring alterations in serum proteome during the febrile, defervescence and convalescent stages has not been reported hitherto. Here, we report, for the first time, serum proteomic alterations in a longitudinal cohort of P. vivax infected patients to elucidate host responses when fever is established (temperature of the body reaches above higher normal level), during the stage when the temperature comes down to normal, and also during the gradual recovery of health after the illness. The three stages discussed in our study have been categorically chosen depending upon the clinical course of uncomplicated vivax malaria. Analysis of the early febrile stage represents host proteome profile immediately after onset of the infection, without any effect of anti-malarial drugs. The second, defervescence stage, reflects any immediate change in blood proteome at early recovery phase, while the convalescent stage indicates a phase after administration of 14 days radical cure treatment with primaquine and a complete recovery, when none of the patients displayed any apparent symptoms of malaria. We have also performed an extensive quantitative proteomics analysis to compare the serum proteome profiles of vivax malaria patients with low and moderately-high parasitemia with healthy community controls. Isobaric tags for relative and absolute quantitation (iTRAQ) and 2-D fluorescence difference gel electrophoresis (2D-DIGE)-based quantitative proteomics approaches were used in the discovery-phase of the study, and some selected differentially abundant serum proteins were validated further by using ELISA. Interestingly, some of the serum proteins like Serum amyloid A, Apolipoprotein A1, C-reactive protein, Titin and Haptoglobin, were found to be sequentially altered with respect to increased parasite counts, while many of the quantified candidates such as Hemopexin, Vitronectin, Clusterin and Apolipoprotein E exhibited nearly equal levels of differential serum abundance in different parasitemic malaria patients. Analysis of a longitudinal cohort of malaria patients indicated reversible alterations in serum levels of some proteins such as Haptoglobin, Apolipoprotein E, Apolipoprotein A1, Carbonic anhydrase 1, and Hemoglobin subunit alpha upon treatment; however, the levels of a few other proteins did not return to the baseline even during the convalescent phase of the infection. Identification of the differentially abundant serum proteins and associated physiological pathways in vivax malaria along with phase-specific protein profiles during the acute and convalescent phases of the infection can effectively enhance our understanding of P. vivax disease biology and host immune responses.
2018-10-26 | PXD005267 | Pride