Parasite load in the blood and skin of dogs naturally infected by Leishmania infantum is correlated with their capacity to infect sand fly vectors

AbstractThe sand fly Lutzomyia longipalpis is primarily responsible for the transmission of visceral leishmaniasis (VL) in the New World, and dogs are considered to be the main urban reservoir of this disease. In order to improve the efficacy of control measures, it is essential to assess the transmission capacity of Leishmania infantum to the sand fly vector by naturally infected dogs. The present study investigated the existence of correlations between canine clinical presentation and the intensity of parasite load in the blood, skin and spleen of naturally infected dogs. In addition, we also attempted to establish correlations between the intensity of parasite load in canine tissue and the parasite load detected in sandflies five days after feeding on naturally infected dogs. A total of 23 dogs were examined and classified according to clinical manifestation of canine VL. Blood samples, splenic aspirate and skin biopsies were collected and parasite DNA was quantified by qPCR. Canine capacity to infect Lu. longipalpis with parasites was evaluated by xenodiagnosis and parasite loads were measured five days after feeding. No significant differences were observed with respect to canine clinical manifestation and the parasite loads detected in the blood, skin and spleen samples obtained from naturally infected dogs. Regardless of clinical canine visceral leishmaniasis (CVL) presentation and the degree of parasite burden, almost half of the dogs successfully infected sandflies with parasites, albeit to a low number of sandflies with correspondingly low parasite loads. Parasite loads in both canine blood and skin were shown to be positively correlated with the canine infectiousness to the sand fly vector, and positive correlations were also observed with respect to these tissues and the sand fly infection rate, as well as the parasite load detected in sandflies following xenodiagnosis. In conclusion, this indicates that parasite loads in both blood and skin can function as potentially reliable markers of canine capacity to infect sand fly vector

Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy

Chronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoan Trypanosoma cruziit is estimated that 10-30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein from T. cruzi named P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein's direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate that T. cruzi P21 is an attractive target for the development of innovative therapeutic agents against CCC.Univ Fed Sao Paulo, Escola Paulista Med, Departamento Microbiol Imunol Parasitol, BR-05508 Sao Paulo, SP, BrazilUniv Fed Uberlandia, Inst Ciencias Biomed, Dept Imunol, Lab Tripanosomatideos, Uberlandia, MG, BrazilUniv Fed Uberlandia, Inst Genet & Bioquim, Lab Bioquim & Toxinas Animais, Uberlandia, MG, BrazilCeTICS, Inst Butantan, Sao Paulo, BrazilUniv Fed Uberlandia, Fac Med, Centro Referencia Nacl Dermatol Sanitaria Hanseni, Lab Patol Mol & Biotecnol, Uberlandia, MG, BrazilUniv Fed Uberlandia, Inst Ciencias Biomed, Dept Immunol, Lab Osteoimunol & Imunol Tumores, Uberlandia, MG, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Departamento Microbiol Imunol Parasitol, BR-05508 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Departamento Microbiol Imunol Parasitol, BR-05508 Sao Paulo, SP, BrazilWeb of Scienc

Immunization of Experimental Dogs With Salivary Proteins From Lutzomyia longipalpis, Using DNA and Recombinant Canarypox Virus Induces Immune Responses Consistent With Protection Against Leishmania infantum

Metacyclic Leishmania promastigotes are transmitted by sand flies that inject parasites and saliva into the host's skin. Previous studies have demonstrated that DNA plasmids encoding Lutzomyia longipalpis salivary proteins LJM17 and LJL143, when used to immunize dogs, resulted in a systemic and local Th1 cell-mediated immunity that interfered in parasite survival in vitro. Here we evaluated the ability of these same salivary antigens to induce anti-Leishmania immunity and to confer protection by immunizing dogs using a novel vaccination strategy more suitable for use in the field. The strategy consisted of a single dose of plasmid followed by two doses of recombinant Canarypoxvirus (rCanarypoxvirus) expressing L. longipalpis salivary proteins (LJM17 or LJL143). Thirty days after the final immunization, dogs were intradermally challenged with 107Leishmania infantum promastigotes in the presence of L. longipalpis saliva. We followed the experimentally infected dogs for 10 months to characterize clinical, parasitological, and immunological parameters. Upon vaccination, all immunized dogs presented strong and specific humoral responses with increased serum concentrations of IFN-γ, TNF, IL-7, and IL-15. The serum of dogs immunized with LJM17 also exhibited high levels of IL-2, IL-6, and IL-18. L. infantum infection was established in all experimental groups as evidenced by the presence of anti-Leishmania IgG, and by parasite detection in the spleen and skin. Dogs immunized with LJM17-based vaccines presented higher circulating levels of IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-18, TNF, CXCL10, and GM-CSF post-infection when compared with controls. Results demonstrated that relevant Leishmania-specific immune responses were induced following vaccination of dogs with L. longipalpis salivary antigen LJM17 administered in a single priming dose of plasmid DNA, followed by two booster doses of recombinant Canarypox vector. Importantly, a significant increase in pro-inflammatory cytokines and chemokines known to be relevant for protection against leishmaniasis was evidenced after challenging LJM17-vaccinated dogs as compared to controls. Although similar results were observed following immunization with LJL143, the pro-inflammatory response observed after immunization was attenuated following infection. Collectively, these data suggest that the LJM17-based vaccine induced an immune profile consistent with the expected protective immunity against canine leishmaniosis. These results clearly support the need for further evaluation of the LJM17 antigen, using a heterologous prime-boost vaccination strategy against canine visceral leishmaniosis (CVL)

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Síndrome de DiGeorge (deleção do cromossomo 22q11.2): manejo e prognóstico

A síndrome de DiGeorge (SDG), também conhecida como síndrome velocardiofacial, é uma condição neurogenética autossômica dominante de interesse global caracterizada pela microdeleção do cromossomo 22q11.2, na qual não há predileção por gênero ou raça. A doença é conhecida pela tríade clássica as cardiopatias congênitas, timo hipoplásico – ou aplásico – e hipocalcemia decorrente da hipoplasia paratireoidiana O diagnóstico da síndrome baseia-se em dois exames laboratoriais, a Hibridização Genômica Comparativa baseada em microarray (aCGH) e a Hibridização por Fluorescência in situ (FISH), ambas com a finalidade de investigar o distúrbio genético e o tratamento consiste em tratar as alterações decorrentes da patologia. O objetivo estudo é analisar o manejo e o prognóstico da síndrome de DiGeorge por meio de um apanhado de casos clínicos. Trata-se de uma revisão bibliográfica integrativa, de natureza quantitativa, que utilizou as plataformas PubMed (Medline), Scientific Eletronic Library On-line (SciELO) e Cochrane Library como bases de dados para a seleção dos artigos, todos na língua inglesa. Foram utilizadas literaturas publicadas com recorte temporal de 2017 a 2022. De acordo com as literaturas analisadas, foi observado que a SDG requer diligência por parte dos profissionais da saúde no que concerne ao seu manejo, vide os vários fenótipos, desde leves a graves, da patologia. Por ter envolvimento multissistêmico, é essencial que, mesmo antes do diagnóstico, os distúrbios inerentes à síndrome sejam tratados e sujeitos à suspeição por intermédio da equipe, a qual necessita ter conhecimento acerca dessa possibilidade, haja vista a eventualidade de um pior prognóstico aos pacientes portadores

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

A docking-based structural analysis of geldanamycin-derived inhibitor binding to human or Leishmania Hsp90

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-11-14T13:03:57Z No. of bitstreams: 1 Palma, L. C. A docking....pdf: 2316481 bytes, checksum: 4b22ab5fe091a63eb03467552d28b571 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-11-14T13:31:09Z (GMT) No. of bitstreams: 1 Palma, L. C. A docking....pdf: 2316481 bytes, checksum: 4b22ab5fe091a63eb03467552d28b571 (MD5)Made available in DSpace on 2019-11-14T13:31:09Z (GMT). No. of bitstreams: 1 Palma, L. C. A docking....pdf: 2316481 bytes, checksum: 4b22ab5fe091a63eb03467552d28b571 (MD5) Previous issue date: 2019-01-14Conselho Nacional de Pesquisa e Desenvolvimento Científico (P.S.T.V. – Universal 422867/2016-0 http://www.cnpq.br) and Fundação de Amparo a Ciência e Tecnologia do Estado de Pernambuco (LFGRF – BFP-0063-4.03/17). P.S.T.V. holds a grant from CNPq for productivity in research (307832/2015-5).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita Interação e Epidemiologia do Hospedeiro. Salvador, BA, Brasil.Federal University of Pernambuco. Department of Pharmaceutical Sciences. Recife, PE, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita Interação e Epidemiologia do Hospedeiro. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita Interação e Epidemiologia do Hospedeiro. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita Interação e Epidemiologia do Hospedeiro. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia de Tecidos e Imunofarmacologia. Salvador, BA, Brasil.Federal University of Pernambuco. Department of Pharmaceutical Sciences. Recife, PE, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita Interação e Epidemiologia do Hospedeiro. Salvador, BA, Brasil.Leishmaniasis is a neglected disease that affects millions of individuals around the world. Regardless of clinical form, treatment is based primarily on the use of pentavalent antimonials. However, such treatments are prolonged and present intense side effects, which lead to patient abandonment in many cases. The search for chemotherapeutic alternatives has become a priority. Heat Shock Protein 90 (Hsp90) inhibitors have recently come under investigation due to antiparasitic activity in Plasmodium sp., Trypanosoma sp. and Leishmania sp. Some of these inhibitors, such as geldanamycin and its analogs, 17-AAG and 17-DMAG, bind directly to Hsp90, thereby inhibiting its activity. Previous studies have demonstrated that different parasite species are more susceptible to some of these inhibitors than host cells. We hypothesized that this increased susceptibility may be due to differences in binding of Hsp90 inhibitors to Leishmania protein compared to host protein. Based on the results of the in silico approach used in the present study, we propose that geldanamycin, 17-AAG and 17-DMAG present an increased tendency to bind to the N-terminal domain of Leishmania amazonensis Hsp83 in comparison to human Hsp90. This could be partially explained by differences in intermolecular interactions between each of these inhibitors and Hsp83 or Hsp90. The present findings demonstrate potential for the use of these inhibitors in the context of anti-Leishmania therapy