Apoptosis of non-parasitized red blood cells in malaria: a putative mechanism involved in the pathogenesis of anaemia

<p>Abstract</p> <p>Background</p> <p>Severe anaemia is a common complication of <it>Plasmodium falciparum </it>malaria in hyperendemic regions. Premature elimination of non-parasitized red blood cells (nRBC) has been considered as one mechanism involved in the genesis of severe malaria anaemia. It has been reported that apoptosis can occur in RBC and, consequently, this cell death process could contribute to anaemia. This study was performed to evaluate the susceptibility of nRBC to apoptosis in a malaria anaemia murine model.</p> <p>Methods</p> <p>Balb/c mice were intraperitonially inoculated with 1 × 10⁶<it>P. yoelii </it>17XL parasitized RBC (pRBC) and, then, parasitaemia and anaemia were monitored. Apoptosis in both pRBC and nRBC was assessed during early and late phases of infection by flow cytometry using Syto 16 and annexin V-PE double staining and forward scatter measurement.</p> <p>Results</p> <p>As expected, experimental infection of Balb/c mice with <it>Plasmodium yoelii </it>17XL parasites was characterized by progressive increase of parasitaemia and acute anaemia, leading to death. Flow cytometry analysis showed that a number of pRBC was in the apoptotic process. It was noteworthy that the increase of nRBC apoptosis levels occurred in the late phase of infection, when anaemia degree was notably accentuated, while no significant alteration was observed in the early phase.</p> <p>Conclusion</p> <p>The increased levels of nRBC apoptosis herein firstly reported, in malaria infection could represent a putative mechanism worsening the severity of malarial anaemia.</p

Polyclonal B-cell activation in human malaria: relevance to the development of anti-sporozoite specific immune response and of immunopathology in individuals from endemic areas (Rondonia State - Brazil)

Submitted by Sandra Infurna ([email protected]) on 2019-11-06T13:58:05Z No. of bitstreams: 1 ClaudioTD_Ribeiro_etal_IOC_1988.pdf: 290888 bytes, checksum: 7adcc5b866ba2f6d06cc2cc9d40bb169 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-11-06T14:16:46Z (GMT) No. of bitstreams: 1 ClaudioTD_Ribeiro_etal_IOC_1988.pdf: 290888 bytes, checksum: 7adcc5b866ba2f6d06cc2cc9d40bb169 (MD5)Made available in DSpace on 2019-11-06T14:16:46Z (GMT). No. of bitstreams: 1 ClaudioTD_Ribeiro_etal_IOC_1988.pdf: 290888 bytes, checksum: 7adcc5b866ba2f6d06cc2cc9d40bb169 (MD5) Previous issue date: 1988Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil

Immunogenicity and antigenicity of the N-term repeat amino acid sequence of the Plasmodium falciparum P126 antigen

The P126 protein, a parasitosphorus vacuole antigen of Plasmodium falciparum has beenshoen to induce protective immunity in Saimiri and Aotus monkeys. In the present work we investigated its immunogenicity. Our results suggest that the N-term of P126 is poorly immunogenic and antibody response against the P126 could be under a MHC restricted control in C57BL/6(H-2b) mice, which could be problematic in ternms of a use of the P126 in a vaccine program. However, we observed that a synthetic peptide, copying the 6 octapeptide repeat corresponding to the N-term of the P126, induces an antibody response to the native molecule in C57BL/6 non-responder mice. Moreover, the vaccine-P126 recombinant induced anmtibodies against the N-term of the molecule in rabbits while the unprocessed P126 did not

CYP2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region

Funding Information: We acknowledge the participants in the study, without whom this research could not have been done. For laboratorial support the authors wish to show their appreciation to Gabriel Barbosa de Abreu (in memorian). To Norman Ratcliffe for the English revision of this manuscript. Part of this work is described in a Master?s Dissertation by PS, conducted at the Applied Microbiology and Parasitology Post-graduation Program, Federal Fluminense University. Publisher Copyright: © Copyright © 2021 Salles, Perce-da-Silva, Rossi, Raposo, Ramirez Ramirez, Pereira Bastos, Pratt-Riccio, Cassiano, Baptista, Cardoso, Banic and Machado.Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals from the Brazilian Amazon region. The blood samples were collected from 220 unrelated Plasmodium vivax patients from five different endemic areas. Genotyping was performed using SNaPshot® and real-time polymerase chain reaction methods. In all five areas, the rs1065852 (CYP2D6*10, C.100C > T), rs3892097 (CYP2D6*4, 1846C > T) and rs16947 (CYP2D6*2, C.2850G > A), as a homozygous genotype, showed the lowest frequencies. The rs28371725 (CYP2D6*41, 2988G > A) homozygous genotype was not detected, while the allele A was found in a single patient from Macapá region. No deviations from Hardy-Weinberg equilibrium were found, although a borderline p-value was observed (p = 0.048) for the SNP rs3892097 in Goianésia do Pará, Pará state. No significant associations were detected in these frequencies among the five studied areas. For the SNP rs3892097, a higher frequency was observed for the C/T heterozygous genotype in the Plácido de Castro and Macapá, Acre and Amapá states, respectively. The distribution of the CYP2D6 alleles investigated in the different areas of the Brazilian Amazon is not homogeneous. Further investigations are necessary in order to determine which alleles might be informative to assure optimal drug dosing recommendations based on experimental pharmacogenetics.publishersversionpublishe

Genetic polymorphism of the serine rich antigen N-terminal region in Plasmodium falciparum field isolates from Brazil

In this work we investigated the frequency of polymorphism in exon II of the gene encoding most of the amino-terminal region of the serine rich antigen (SERA) in Plasmodium falciparum field samples. The blood samples were colleted from P. falciparum infected individuals in three areas of the Brazilian Amazon. Two fragments have been characterized by polymerase chain reaction: one of 175 bp corresponding to the repeat region with 5 octamer units and one other of 199 bp related to the 6 repeat octamer units of SERA protein. The 199 bp fragment was the predominant one in all the studied areas. The higher frequency of this fragment has not been described before and could be explained by an immunological selection of the plasmodial population in the infected individuals under study. Since repeat motifs in the amino-terminal region of SERA contain epitopes recognized by parasite-inhibitor antibodies, data reported here suggest that the analysis of the polymorphism of P. falciparum isolates in different geographical areas is a preliminary stage before the final drawing of an universal vaccine against malaria can be reached

Evaluation of the genetic polymorphism of Plasmodium falciparum P126 protein (SERA or SERP) and its influence on naturally acquired specific antibody responses in malaria-infected individuals living in the Brazilian Amazon

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>P126 protein is an asexual blood-stage malaria vaccine candidate antigen. Antibodies against P126 are able to inhibit parasite growth <it>in vitro</it>, and a major parasite-inhibitory epitope has been recently mapped to its 47 kDa N-terminal extremity (octamer repeat domain – OR domain). The OR domain basically consists of six octamer units, but variation in the sequence and number of repeat units may appear in different alleles. The aim of the present study was to investigate the polymorphism of P126 N-terminal region OR domain in <it>P. falciparum </it>isolates from two Brazilian malaria endemic areas and its impact on anti-OR naturally acquired antibodies.</p> <p>Methods</p> <p>The study was carried out in two villages, Candeias do Jamari (Rondonia state) and Peixoto de Azevedo (Mato Grosso state), both located in the south-western part of the Amazon region. The repetitive region of the gene encoding the P126 antigen was PCR amplified and sequenced with the di-deoxy chain termination procedure. The antibody response was evaluated by ELISA with the Nt47 synthetic peptide corresponding to the P126 OR-II domain.</p> <p>Results</p> <p>Only two types of OR fragments were identified in the studied areas, one of 175 bp (OR-I) and other of 199 bp (OR-II). A predominance of the OR-II fragment was observed in Candeias do Jamari whereas in Peixoto de Azevedo both fragments OR-I and OR-II were frequent as well as mixed infection (both fragments simultaneously) reported here for the first time. Comparing the DNA sequencing of OR-I and OR-II fragments, there was a high conservation among predicted amino acid sequences of the P126 N-terminal extremity. Data of immune response demonstrated that the OR domain is highly immunogenic in natural conditions of exposure and that the polymorphism of the OR domain does not apparently influence the specific immune response.</p> <p>Conclusion</p> <p>These findings confirm a limited genetic polymorphism of the P126 OR domain in <it>P. falciparum </it>isolates and that this limited genetic polymorphism does not seem to influence the development of a specific humoral immune response to P126 and its immunogenicity in the studied population.</p

The influence of intestinal parasites on Plasmodium vivax-specific antibody responses to MSP-119 and AMA-1 in rural populations of the Brazilian Amazon

Abstract\ud \ud Background\ud Polyparasitism is a common condition in humans but its impact on the host immune system and clinical diseases is still poorly understood. There are few studies of the prevalence and the effect of malaria-intestinal parasite co-infections in the immune response to malaria vaccine candidates. The present study determines whether the presence of malaria and intestinal parasites co-infection is associated with impaired IgG responses to Plasmodium vivax AMA-1 and MSP-119 in a rural population of the Brazilian Amazon.\ud \ud \ud Methods\ud A cross-sectional survey was performed in a rural area of Rondonia State and 279 individuals were included in the present study. At recruitment, whole blood was collected and Plasmodium and intestinal parasites were detected by microscopy and molecular tests. Blood cell count and haemoglobin were also tested and antibody response specific to P. vivax AMA-1 and MSP-119 was measured in plasma by ELISA. The participants were grouped according to their infection status: singly infected with Plasmodium (M); co-infected with Plasmodium and intestinal parasites (CI); singly infected with intestinal parasites (IP) and negative (N) for both malaria and intestinal parasites.\ud \ud \ud Results\ud The prevalence of intestinal parasites was significantly higher in individuals with malaria and protozoan infections were more prevalent. IgG antibodies to PvAMA-1 and/or PvMSP-119 were detected in 74 % of the population. The prevalence of specific IgG was similar for both proteins in all four groups and among the groups the lowest prevalence was in IP group. The cytophilic sub-classes IgG1 and IgG3 were predominant in all groups for PvAMA-1 and IgG1, IgG3 and IgG4 for PvMSP-119. In the case of non-cytophilic antibodies to PvAMA-1, IgG2 was significantly higher in IP and N group when compared to M and CI while IgG4 was higher in IP group.\ud \ud \ud Conclusions\ud The presence of intestinal parasites, mainly protozoans, in malaria co-infected individuals does not seem to alter the antibody immune responses to P. vivax AMA-1 and MSP-119. However, IgG response to both AMA1 and MSP1 were lower in individuals with intestinal parasites.The authors are in debt to the individuals who participated in this study, the\ud Secretary of Health and Laboratory Central (LACEN) of Rondonia, the local\ud malaria control team in Joana D´Arc settlement for their logistic support\ud and the Institute Oswaldo Cruz (Fiocruz) for overall support. This work was\ud supported by PRONEX Malaria network funded by the Brazilian Ministry of\ud Science and Technology (MCT), Conselho Nacional de Desenvolvimento\ud Cientifico e Tecnologico (CNPq, Brazil) and Fundação de Amparo à Pesquisa\ud do Estado do Rio de Janeiro (FAPERJ, Brazil). PROEP, Instituto Oswaldo Cruz\ud (FIOCRUZ, Brazil). JOF is recipient of a Research Productivity Fellowship from\ud CNPq, JCSA is recipient of a fellowship from Instituto Oswaldo Cruz and VAR,\ud MM from CNPq

Polyclonal B-cell activation in human malaria: relevance to the development of anti-sporozoite specific immune response and of immunopathology in individuals from endemic areas (Rondonia State - Brazil)

Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil

Polyclonal B-Lymphocyte activation and sensitization of erythrocytes by IgG in human malaria: relevance to the development of anaemia in a Holoendemic area in northwestern Brazil (Ariquemes - Rondônia)

Submitted by Sandra Infurna ([email protected]) on 2019-11-06T14:45:13Z No. of bitstreams: 1 DalmaBanic_ClaudioTRibeiro_etal_IOC_1986.pdf: 474156 bytes, checksum: 4db4e2c864af6ed53ada3885f343e130 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-11-06T15:01:09Z (GMT) No. of bitstreams: 1 DalmaBanic_ClaudioTRibeiro_etal_IOC_1986.pdf: 474156 bytes, checksum: 4db4e2c864af6ed53ada3885f343e130 (MD5)Made available in DSpace on 2019-11-06T15:01:09Z (GMT). No. of bitstreams: 1 DalmaBanic_ClaudioTRibeiro_etal_IOC_1986.pdf: 474156 bytes, checksum: 4db4e2c864af6ed53ada3885f343e130 (MD5) Previous issue date: 1986Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Investigação e Formação em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Investigação e Formação em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Investigação e Formação em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Investigação e Formação em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil