A5023694981- Heme Oxygenase-1 and Carbon Monoxide
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Malaria Research and Control
- Mosquito-borne diseases and control
- Immune cells in cancer
- Trypanosoma species research and implications
- Tuberculosis Research and Epidemiology
- Neonatal Health and Biochemistry
- Erythrocyte Function and Pathophysiology
- Trace Elements in Health
- Gut microbiota and health
- Viral Infections and Vectors
- Research on Leishmaniasis Studies
- Escherichia coli research studies
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Cannabis and Cannabinoid Research
- Hemoglobin structure and function
- Endoplasmic Reticulum Stress and Disease
- Toxoplasma gondii Research Studies
- Probiotics and Fermented Foods
Instituto Gulbenkian de Ciência
2014-2025
Universidade de São Paulo
2024
Calouste Gulbenkian Foundation
2007-2020
Infraestruturas de Portugal (Portugal)
2005
Universidade Federal da Bahia
2001-2003
Fundação Oswaldo Cruz
1987-2003
Heme from red blood cells released in septic shock worsens organ dysfunction and increases the risk of death, but can be overcome by a scavenger free heme.
Heme oxygenase-1 (HO-1, encoded by HMOX1) dampens inflammatory reactions via the catabolism of heme into CO, Fe, and biliverdin. We report that expression HO-1 dictates pathologic outcome experimental autoimmune encephalomyelitis (EAE), a model multiple sclerosis (MS). Induction EAE in Hmox1(-/- )C57BL/6 mice led to enhanced CNS demyelination, paralysis, mortality, as compared with Hmox1(+/+) mice. cobalt protoporphyrin IX (CoPPIX) administration after onset reversed paralysis C57BL/6 SJL/J...
Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance a defense strategy against infection that preserves homeostasis without exerting direct negative impact on pathogens. Here, we demonstrate induction of the iron-sequestering ferritin H chain (FTH) in response polymicrobial infections critical establish disease sepsis. The protective effect FTH exerted via mechanism counters iron-driven...
A greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium tuberculosis (Mtb). We have shown systemic administration Bacille Calmette-Guérin (BCG) or β-glucan reprograms HSCs in the bone marrow (BM) via a type II interferon (IFN-II) interleukin-1 (IL1) response, respectively, which confers trained against Mtb. Here, we demonstrate that, unlike BCG...
We asked whether the neuroprotective effect of cholinergic microglial stimulation during an ischemic event acts via a mechanism involving activation nuclear factor erythroid-2-related 2 (Nrf2) and/or expression its target cytoprotective gene, heme oxygenase-1 (HO-1). Specifically, protective pharmacologic alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonist PNU282987 was analyzed in organotypic hippocampal cultures (OHCs) subjected to oxygen and glucose deprivation (OGD) vitro as well...
Multicellular organisms rely on inter-organ communication networks to maintain vital parameters within a dynamic physiological range. Macrophages are central this homeostatic control system, sensing deviations of those and responding accordingly support tissue function organismal homeostasis. Here we demonstrate that dysregulation iron metabolism in parenchyma cells, imposed by the deletion ferritin H chain, is sensed monocyte-derived macrophages. In response, macrophages derived from...
Malaria, the disease caused by Plasmodium spp. infection, remains a major global cause of morbidity and mortality. Host protection from malaria relies on immune-driven resistance mechanisms that kill However, these are not sufficient per se to avoid development severe forms disease. This is accomplished instead via establishment tolerance malaria, defense strategy does target directly. Here we demonstrate tissue damage-control mechanism operates specifically in renal proximal tubule...
The proinflammatory cytokine interleukin 1 (IL-1) is crucially involved in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Herein, we studied role IL-1 signaling blood-brain barrier (BBB) endothelial cells (ECs), astrocytes microglia for EAE development, using mice with conditional deletion receptor IL-1R1. We found that redundant development EAE, whereas IL-1R1 BBB-ECs markedly ameliorated disease severity. upregulated...
Abstract Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of TREG cell lineage relies on sustained FOXP3 mechanism involving demethylation cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in locus. This cytosine is catalyzed ten–eleven translocation (TET) family dioxygenases, and it involves redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish...
Nitric oxide (NO) and carbon monoxide (CO) are gasotransmitters that suppress the development of severe forms malaria associated with Plasmodium infection. Here, we addressed mechanism underlying their protective effect against experimental cerebral (ECM), a form develops in Plasmodium-infected mice, which resembles, many aspects, human (CM). NO suppresses pathogenesis ECM via involving (1) transcription factor nuclear erythroid 2-related 2 (NRF-2), (2) induction heme oxygenase-1 (HO-1), (3)...
The ferritin heavy/heart chain (FTH) gene encodes the ferroxidase component of iron (Fe) sequestering complex, which plays a central role in regulation cellular Fe metabolism. Here we tested hypothesis that regulates organismal metabolism manner impacts energy balance and thermal homeostasis.We developed mouse strain, referred herein as FthR26 fl/fl, expressing tamoxifen-inducible Cre recombinase under control Rosa26 (R26) promoter carrying two LoxP (fl) sites: one at 5'end Fth another 3'...
Abstract The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a transmembrane heme exporter essential for embryonic vascular development. However, the exact role of FLVCR1a during blood vessel development remains largely undefined. Here, we show that highly expressed in angiogenic endothelial cells (ECs) compared to quiescent ECs. Consistently, ECs lacking give rise structurally and functionally abnormal networks multiple models developmental pathologic angiogenesis. Firstly,...
Severe presentations of malaria emerge as Plasmodium (P.) spp. parasites invade and lyse red blood cells (RBC), producing extracellular hemoglobin (HB), from which labile heme is released. Here, we tested whether scavenging HB and/or heme, by haptoglobin (HP) hemopexin (HPX), respectively, counter the pathogenesis severe malaria. We found that circulating an independent risk factor for cerebral non-cerebral P. falciparum in children. Labile was negatively correlated with HP HPX, were,...
Iron recycling prevents the development of anemia under homeostatic conditions. Whether iron was co-opted as a defense strategy to prevent in response infection is unclear. We find that severe Plasmodium falciparum malaria, onset life-threatening associated with acute kidney injury (AKI), irrespective parasite load. Using well-established experimental rodent model malaria anemia, we identify transcriptional endows renal proximal tubule epithelial cells (RPTECs) capacity store and recycle...
Whether jaundice, a common presentation of Plasmodium ( P .) falciparum malaria (1-3) arising from the accumulation circulating bilirubin, represents an adaptive or maladaptive response to spp. infection is not understood (1-3). We found that asymptomatic P. was associated with >10-fold higher ratio unconjugated bilirubin over parasite burden, compared symptomatic malaria. Genetic suppression synthesis by biliverdin reductase A (BVRA) (4) increased virulence and mortality in mice....
ABSTRACT The initial encounter of Leishmania cells and from the immune system is fundamentally important in outcome infection determines disease development or resistance. We evaluated anti- amazonensis response naive volunteers by using an vitro priming (IVP) comparing responses following vivo vaccination against same parasite. In stimulation allowed us to distinguish two groups individuals, those who produced small amounts gamma interferon (IFN-γ) ( n = 16) (low producers) large this...
Sickle cell disease has a worldwide distribution and is public health problem in Brazil. Although vaso-occlusive crisis (VOC) one of the most important clinical features disease, there are still several steps its pathogenesis which unknown. The increase chemotactic factor interleukin 8 (IL-8) been reported to be involved sickle crisis, but this not demonstrated conclusively. In present study we analyzed serum IL-8 levels by ELISA hematological parameters hemoglobin patterns standard...
We compared the distribution patterns of individual Plasmodium species and mixed-species infections in two geographically close endemic areas, but showing environmental differences.Comparisons concerned circulating both human mosquito vector populations dry wet seasons, at a microepidemiological level (households).Both areas revealed very high overall prevalence infection, all year-round age groups.Plasmodium falciparum was predominant species, being found vast majority infected individuals...
Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red cells (RBCs) inflammation. Here, we show that heme oxygenase-1 (HO-1), pleiotropic cytoprotective isoenzyme mitigates heme-mediated tissue damage, is induced after bites sand flies, mosquitoes, ticks. Further, demonstrate erythrophagocytosis by macrophages, including skin-residing CD163+CD91+ professional iron-recycling subpopulation, produces HO-1 bites. Importantly, establish...
Genes encoding glycosyltransferases can be under relatively high selection pressure, likely due to the involvement of glycans synthesized in host-microbe interactions. Here, we used mice as an experimental model system investigate whether loss α-1,3-galactosyltransferase gene (