Biology subjects

Siles-Lucas, M.

Publications and source records attributed to Siles-Lucas, M..

3 recordsLinked to original sources

bioRxiv2024

Inflammation cellular platform (INCEPLAT) for testing anti-inflammatory compounds for SARS-CoV-2

From the early days of the COVID-19 pandemic, an excessive release of proinflammatory cytokines, such as IL6, was detected in serum from patients. As a consequence, several anti-inflammatory drugs, such as Dexamethasone (a strong corticoid), were used to counteract such cytokine storm occurring during severe disease. By contrast, pro-inflammatory interleukin 11 (IL11), a member of the IL6 family, was detected in respiratory tissues from infected patients and in experimental epithelial cellular models. In this work, human A549 lung epithelial cells were individually transduced with SARS-CoV-2 open reading frames (ORFs), resulting in a IL11 increase, which was significantly decreased after Dexamethasone treatment. The use of this cellular platform allowed us to screen for new possible anti-inflammatory compounds from Fasciola hepatica. Our results highlighted the ability of FhNEJ (Fasciola hepatica newly excysted juvenile flukes) somatic extract to decrease IL11 levels in ORF-transduced cells. These results emphasized the role of IL11 in lung epithelial inflammation, making it a potential target for future treatments of lung inflammation which occurs in COVID-19, and validate the use of these ORF-expressing cells as a cellular platform to test anti-inflammatory compounds for COVID-19 disease.

immunology↗

bioRxiv2022

Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism

BackgroundThe trematode Fasciola hepatica is the most widespread causative agent of fasciolosis, a parasitic disease that mainly affects humans and ruminants worldwide. During F. hepatica infection, newly excysted juveniles (FhNEJ) emerge in the duodenum of the mammalian host and migrate towards the definitive location of the parasite, the intra-hepatic biliary ducts. Understanding how F. hepatica traverses the intestinal wall and migrates towards the liver is pivotal for the development of more successful strategies against fasciolosis. The central enzyme of the mammalian fibrinolytic system is plasmin, a serine protease whose functions are exploited by a number of parasite species owing to its broad spectrum of substrates, including components of tissue extracellular matrices. The aim of the present work is to understand whether FhNEJ co-opt the functions of their host fibrinolytic system as a mechanism to facilitate trans-intestinal migration. Methodology/Principal FindingsAn FhNEJ tegument protein extract (FhNEJ-Teg) was obtained in vitro, and its capability to bind the zymogen plasminogen (PLG) and enhance its conversion to the active protease, plasmin, were analyzed by a combination of enzyme-linked immunosorbent, chromogenic and immunofluorescence assays. Additionally, PLG-binding proteins in FhNEJ-Teg were identified by 2D electrophoresis coupled to mass-spectrometry analysis, and the interactions were validated using FhNEJ recombinant proteins. Conclusions/SignificanceOur results show that FhNEJ-Teg contains proteins that bind PLG and stimulate its activation to plasmin, which could facilitate the traversal of the intestinal wall by FhNEJ and contribute to the successful establishment of the parasite within its mammalian host. Altogether, our findings contribute to a better understanding of host-parasite relationships during early fasciolosis and may be exploited from a pharmacological and/or immunological perspective for the development of treatment and control strategies against this global disease. Author SummaryFasciolosis is a disease caused by parasites of the genus Fasciola, of which F. hepatica stands out as it has successfully spread all over the world and infects humans and animals throughout the entire global geography. Definitive hosts become infected by ingestion of aquatic plants or water contaminated with metacercariae, which excyst in the duodenum and release the so-called newly excysted juvenile flukes (FhNEJ). FhNEJ traverse the intestinal wall and evolve into immature parasites that migrate through the peritoneum and liver parenchyma until they reach their definitive location inside the major biliary ducts, where adult worms develop and egg shedding starts. In order to cross the intestinal wall, FhNEJ are endowed with a repertoire of proteases that degrade components of the intestinal extracellular matrix, and we hypothesized that they may also co-opt the proteolytic functions of plasmin, the central enzyme of the mammalian fibrinolytic system, to migrate more efficiently across host tissues. In this study, we demonstrate that FhNEJ express proteins on their tegument surface that interact with plasminogen, the zymogen of plasmin, and stimulate its conversion into its active form, which could potentially be used for trans-intestinal migration and contribute to the successful establishment of the parasite within its mammalian host.

molecular biology↗

bioRxiv2019

Potential risk factors associated with human cystic echinococcosis: a semi-structured questionnaire from a large population-based ultrasound cross-sectional study in Eastern Europe and Turkey

BackgroundCystic echinococcosis (CE) is a neglected parasitic zoonosis prioritized by the WHO for control. Hygiene education is included in CE control campaigns but appears of little impact, and the precise risk factors for human infection are still uncertain. Several works investigated potential risk factors for CE through questionnaires, mostly carried out on small samples, providing contrasting results. We present the analysis of risk factors questionnaires administered to participants to the largest prevalence study on CE conducted in Eastern Europe.\n\nMethodology/Principal FindingsA semi-structured questionnaire was administered to 24,687 people from rural Bulgaria, Romania, and Turkey. CE cases were defined individuals with abdominal CE cysts detected on ultrasound. Variables associated with CE infection at p<0.20 in bivariate analysis were included into a multivariable logistic model, with a random effect to account for clustering at village level. Adjusted odds ratio (AOR) with 95%CI were used to describe the strength of associations. Data were weighted to reflect the relative distribution of the rural population in the study area by country, age group and sex. Valid records from 22,027 people were analyzed. According to the main occupation in the past 20 years, \"housewife\" (AOR 3.11 [1.51-6.41]) and \"retired\" (AOR 2.88 [1.09-7.65]) showed significantly higher odds of being infected compared to non-agricultural workers. \"Having relatives with CE\" (AOR 4.18 [1.77-9.88]) was also associated with higher odds of infection. Dog-related and food/water-related factors were not associated with infection.\n\nConclusions/SignificanceOur results point to infection being acquired in a \"domestic\" rural environment and support the view that CE should be considered more a \"soil-transmitted\" than a \"food-borne\" infection, acquired through a \"hand-to-mouth\" mechanism. This result helps delineating the dynamics of infection transmission and have practical implications in the design of specific studies to shed light on actual sources of infection and inform control campaigns.\n\nAUTHOR SUMMARYCystic echinococcosis (CE) is a parasitic disease with high socio-economic impact, mostly affecting pastoral communities. The causative agent, Echinococcus granulosus sensu lato, is naturally transmitted between dogs and livestock; humans acquire infection through accidental ingestion of parasite eggs. Hygiene education is among the strategies of CE control campaigns, but appears of little impact. \"Ingestion of contaminated food/water\", and \"contact with dogs\" are generally mentioned as the sources of human infection, however actual risk factors are still undefined. Several works investigated potential risk factors for human CE infection through questionnaires, mostly carried out on small samples, providing contrasting results. We analysed 22,027 risk factors questionnaires administered to the participants of the largest prevalence study on CE conducted in Eastern Europe. We found that being \"housewife\" and \"retired\" as the main occupation in the past 20 years, and \"having relatives with CE\" were associated with higher odds of CE infection, while dog-related and food/water-related factors were not associated with infection. Our results indicate that CE may be considered more a \"soil-transmitted\" than a \"food-borne\" infection, acquired through a \"hand-to-mouth\" mechanism in a domestic, rural environment. This may help designing specific studies on pathways of transmission of this neglected parasite.

epidemiology↗