The Emerging Role of Complement Lectin Pathway in Trypanosomatids: Molecular Bases in Activation, Genetic Deficiencies, Susceptibility to Infection, and Complement System-Based Therapeutics

The innate immune system is evolutionary and ancient and is the pivotal line of the host defense system to protect against invading pathogens and abnormal self-derived components. Cellular and molecular components are involved in recognition and effector mechanisms for a successful innate immune response. The complement lectin pathway (CLP) was discovered in 1990. These new components at the complement world are very efficient. Mannan-binding lectin (MBL) and ficolin not only recognize many molecular patterns of pathogens rapidly to activate complement but also display several strategies to evade innate immunity. Many studies have shown a relation between the deficit of complement factors and susceptibility to infection. The recently discovered CLP was shown to be important in host defense against protozoan microbes. Although the recognition of pathogen-associated molecular patterns by MBL and Ficolins reveal efficient complement activations, an increase in deficiency of complement factors and diversity of parasite strategies of immune evasion demonstrate the unsuccessful effort to control the infection. In the present paper, we will discuss basic aspects of complement activation, the structure of the lectin pathway components, genetic deficiency of complement factors, and new therapeutic opportunities to target the complement system to control infection

A new landscape of host–protozoa interactions involving the extracellular vesicles world

This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University Press 2018Extracellular vesicles (EVs) are released by a wide number of cells including blood cells, immune system cells, tumour cells, adult and embryonic stem cells. EVs are a heterogeneous group of vesicles (~30–1000 nm) including microvesicles and exosomes. The physiological release of EVs represents a normal state of the cell, raising a metabolic equilibrium between catabolic and anabolic processes. Moreover, when the cells are submitted to stress with different inducers or in pathological situations (malignancies, chronic diseases, infectious diseases.), they respond with an intense and dynamic release of EVs. The EVs released from stimulated cells vs those that are released constitutively may themselves differ, both physically and in their cargo. EVs contain protein, lipids, nucleic acids and biomolecules that can alter cell phenotypes or modulate neighbouring cells. In this review, we have summarized findings involving EVs in certain protozoan diseases. We have commented on strategies to study the communicative roles of EVs during host–pathogen interaction and hypothesized on the use of EVs for diagnostic, preventative and therapeutic purposes in infectious diseases. This kind of communication could modulate the innate immune system and reformulate concepts in parasitism. Moreover, the information provided within EVs could produce alternatives in translational medicine.Peer reviewedFinal Accepted Versio

Complement C2 Receptor Inhibitor Trispanning Confers an Increased Ability to Resist Complement-Mediated Lysis in Trypanosoma cruzi

The ability to resist complement differs between theYand Colombiana Trypanosoma cruzi strains.Wefound that the Y strain of T. cruzi was more able to resist the classical and lectin pathways of complement activation than the Colombiana strain. The complement C2 receptor inhibitor trispanning gene (CRIT) is highly conserved in both strains. At the protein level, CRIT is expressed only in stationary-phase epimastigotes of the Y but not the Colombiana strain and is expressed in infectious metacyclic trypomastigotes of both strains. Y strain epimastigotes with an overexpressed CRIT gene (pTEX-CRIT) had higher survival in normalhumanserum (NHS). Overexpression of the Y strain CRIT gene in Colombiana epimastigote forms increased the parasite's resistance to lysis mediated by the classical and lectin pathways but not to lysis mediated by alternative pathways. CRIT involvement on the parasite surface was confirmed by showing that the lytic activity ofNHSagainst epimastigotes could be restored by adding excess C

Caracterização dos óbitos notificados decorrentes de complicações dos cuidados médicos e cirúrgicos

Objective: describing the cases of deaths reported due to complications of medical and surgical care in Brazil between 2015 to 2018. Method: a descriptive and retrospective conducted between June and July 2020 with the records of deaths extracted from the Health Mortality Information System. The data were grouped into two biennia, 2015-2016, and 2017-2018, and analyzed by descriptive statistics and percentage variations. Results: there were reported 6,587 deaths, especially the 2017-2018 biennium (n=3,425;52%). Deaths caused using medical equipment reduced in Brazil, with a negative percentage variation of 15.4% among the biennia. There was an increase in deaths from adverse effects of drugs/medications with a positive percentage variation of 12.2%. The number of deaths from accidents during hospital care remained stationary. Conclusion: changes were observed in the records of deaths notified in Brazil, and expanding preventive actions aimed at reducing deaths are necessary in all notification groups.Objetivo: describir los casos de muertes reportadas por complicaciones de la atención médica y quirúrgica en Brasil entre 2015 y 2018. Método: descriptivo y retrospectivo realizado entre junio y julio de 2020 con los registros de defunciones extraídos del Sistema de Información de Mortalidad en Salud. Los datos se agruparon en dos bienios 2015-2016 y 2017-2018 y se analizaron mediante estadísticas descriptivas y variaciones porcentuales. Resultados: se reportaron 6.587 muertes, especialmente em el bienio 2017-2018 (n=3.425;52%). Las muertes causadas por el uso de equipo médico se redujeron en Brasil, con una variación porcentual negativa del 15,4% entre los bienios. Hubo un aumento en las muertes por efectos adversos de medicamentos con una variación porcentual positiva de 12.2%. El número de muertes por accidentes durante la atención hospitalaria se mantuvo estacionario. Conclusión: se observaron cambios en los registros de muertes notificadas en Brasil, y es necesario ampliar las acciones preventivas dirigidas a reducir las muertes en todos los grupos de notificación.Objetivo: descrever os casos de óbitos notificados por complicações de assistência médica e cirúrgica no Brasil entre 2015 a 2018. Método: descritivo e retrospectivo conduzido entre junho e julho de 2020 com os registros de óbitos extraídos do Sistema de Informações sobre Mortalidade em Saúde. Os dados foram agrupados em dois biênios 2015-2016 e 2017-2018 e analisados por estatística descritiva e variações percentuais. Resultados: foram notificados 6.587 óbitos, com destaque para o biênio 2017-2018 (n=3.425;52%).  Os óbitos ocasionados pelo uso de equipamentos médicos reduziram no Brasil, com variação percentual negativa de 15,4% entre os biênios. Houve aumento das mortes por efeitos adversos de drogas/medicamentos com variação percentual positiva de 12,2%. O número de óbitos por acidentes durante a assistência hospitalar se manteve estacionário. Conclusão: observaram-se alterações nos registros de óbitos notificados no Brasil, e expandir ações preventivas que visem reduzir os óbitos são necessárias em todos os grupos de notificação

Peptidylarginine Deiminase Inhibition Abolishes the Production of Large Extracellular Vesicles From

is a microaerophilic protozoan that is an important etiologic agent of diarrhea worldwide. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which modulate the physiopathology of giardiasis. Here we describe new features of EV production, revealing its capacity to shed two different enriched EV populations: large (LEV) and small extracellular vesicles (SEV) and identified relevant adhesion functions associated with the larger population. Proteomic analysis revealed differences in proteins relevant for virulence and host-pathogen interactions between the two EV subsets, such as cytoskeletal and anti-oxidative stress response proteins in LEVS. We assessed the effect of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release from . The compounds were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of LEVs and reducing parasite attachment to host cells . Our results suggest that LEVs and SEVs have a different role in host-pathogen interaction, and that treatment with EV-inhibitors may be a novel treatment strategy for recurrent giardiasis. [Abstract copyright: Copyright © 2020 Gavinho, Sabatke, Feijoli, Rossi, da Silva, Evans-Osses, Palmisano, Lange and Ramirez.

Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro

This document is the Accepted Manuscript version of a published work that appeared in final form in European Journal of Cell Biology, after peer review and technical editing by the publisher. To access the final edited and published work see: https://doi.org/10.1016/j.ejcb.2017.01.005.Giardia intestinalis (G.I), is an anaerobic protozoan and the aetiological agent of giardiasis, a diarrhoea present worldwide and associated with poverty. G.I has a simple life cycle alternating between cyst and trophozoite. Cysts are transmitted orally to the stomach and transform to trophozoites in the intestine by a multifactorial process. Recently, microvesicles (MVs) have been found to be released from a wide range of eukaryotic cells. We have observed a release of MVs during the life cycle of G.I., identifying MVs from active trophozoites and from trophozoites differentiating to the cyst form. The aim of the current work was to investigate the role of MVs from G.I in the pathogenesis of giardiasis. MVs from log phase were able to increase the attachment of G. intestinalis trophozoites to Caco-2 cells. Moreover, MVs from G. intestinalis could be captured by human immature dendritic cells, resulting in increased activation and allostimulation of human dendritic cells. Lipid rafts participate in the MV biogenesis and in the attachment to Caco-2 cells. Nevertheless, proteomic analysis from two types of MVs has shown slight differences at the protein levels. An understanding of biogenesis and content of MVs derived from trophozoites might have important implications in the pathogenesis of the disease.Peer reviewe

Microvesicles and exosomes as vehicles between protozoan and host cell communication

Made available in DSpace on 2015-08-19T13:49:31Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) poliana_deolindo_etal_IOC-2013.pdf: 361231 bytes, checksum: 93842d6583f3b14ecf0086171cfdc599 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Biologia Molecular de Parasitas e Vetores. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Biologia Molecular de Parasitas e Vetores. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Biologia Molecular de Parasitas e Vetores. Rio de Janeiro, RJ, Brasil.Cells release extracellular vesicles in response to external factors or in a physiological way. Microvesicles and exosomes originate in cells in different ways and, depending on their contents, may have multiple biological effects on other cells and the environment. The host cell–parasite relationship could be changed dramatically by the plasticity of a new type of communication through extracellular vesicles. In the present paper, we discuss how protozoans use this new resource to evade the immune system and establish infection

Mechanisms of complement lectin pathway activation and resistance by trypanosomatid parasites

Studies in the past decade have demonstrated a crucial role for the complement lectin pathway in host defence against protozoan microbes. Recognition of pathogen surface molecules by mannan-binding lectin and ficolins revealed new mechanisms of innate immune defence and a diversity of parasite strategies of immune evasion. In the present review, we will discuss the current knowledge of: (1) the molecular mechanism of lectin pathway activation by trypanosomes; (2) the mechanisms of complement evasion by trypanosomes; and (3) host genetic deficiencies of complement lectin pathway factors that contribute to infection susceptibility and disease progression. This review will focus on trypanosomatids, the parasites that cause Chagas disease, leishmaniasis and sleeping sickness (African trypanosomiasis)