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2.
Front Immunol ; 13: 906338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958580

RESUMO

Schistosomiasis is a disease of global significance, with severity and pathology directly related to how the host responds to infection. The immunological narrative of schistosomiasis has been constructed through decades of study, with researchers often focussing on isolated time points, cell types and tissue sites of interest. However, the field currently lacks a comprehensive and up-to-date understanding of the immune trajectory of schistosomiasis over infection and across multiple tissue sites. We have defined schistosome-elicited immune responses at several distinct stages of the parasite lifecycle, in three tissue sites affected by infection: the liver, spleen, and mesenteric lymph nodes. Additionally, by performing RNA-seq on the livers of schistosome infected mice, we have generated novel transcriptomic insight into the development of schistosome-associated liver pathology and fibrosis across the breadth of infection. Through depletion of CD11c+ cells during peak stages of schistosome-driven inflammation, we have revealed a critical role for CD11c+ cells in the co-ordination and regulation of Th2 inflammation during infection. Our data provide an updated and high-resolution account of how host immune responses evolve over the course of murine schistosomiasis, underscoring the significance of CD11c+ cells in dictating host immunopathology against this important helminth infection.


Assuntos
Esquistossomose mansoni , Esquistossomose , Animais , Antígeno CD11c , Imunidade , Inflamação , Camundongos , Schistosoma mansoni
3.
PLoS Negl Trop Dis ; 14(5): e0007743, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32374726

RESUMO

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host-parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.


Assuntos
Proteínas de Helminto/genética , Schistosoma mansoni/crescimento & desenvolvimento , Schistosoma mansoni/genética , Esquistossomose mansoni/parasitologia , Animais , Feminino , Proteínas de Helminto/metabolismo , Humanos , Masculino , Camundongos , Schistosoma mansoni/metabolismo , Esquistossomose mansoni/patologia , Transcriptoma
4.
AAS Open Res ; 2: 27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32704620

RESUMO

Background: We aimed at investigating the impact of malaria on the haematological parameters of residents from different demographic settlements in the Ashanti Region of Ghana. Malaria parasites trigger changes in certain haematological parameters, which may result in a number of clinical manifestations. Differences in demographic settlements, such as rural, peri-urban and urban settlements may also influence these changes, but this has not been extensively studied in Ghana. Methods: We conducted a hospital-based, cross-sectional study from January to December 2018 in three different settlements. A total of 598 participants were recruited. Blood smears were examined to detect and quantify malaria parasitaemia, while haematological parameters were measured using a haematology analyser. Results: Participants from the rural settlement had the highest malaria prevalence (21.3%) compared to the urban (11.8%) and peri-urban areas (13.3%); however, the peri-urban area had the highest median parasite density (568; IQR=190.0-1312.0). Age was significantly associated with the odds of malaria positivity (OR: 0.97; CI:0.96 - 0.99). When haematological parameters of the malaria-infected study participants were compared to the parameters of uninfected participants, red blood cell count (p=0.017), haemoglobin (p=0.0165), haematocrit (p=0.0015), mean corpuscular volume (p=0.0014), plateletcrit (p<0.0001) and platelet count (p<0.0001) were all significantly lower in the malaria infected group. In addition to age, haemoglobin and plateletcrit levels were also inversely correlated with the odds of testing positive for malaria, suggesting that children who were anaemic and/or thrombocytopaenic were likely to be infected. After fitting the data to a logistic regression model comprising the three variables, the model correctly categorised 78% of uninfected study participants, but only 50% of the malaria-positive participants. Conclusions: Study participants who were positive for malaria were younger and had low haemoglobin and plateletcrit levels compared to uninfected individuals. Further studies are needed to more precisely elucidate the relationship between malaria infection,demographic and haematological parameters.

5.
AAS Open Res ; 2: 166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32734139

RESUMO

Background: Toxoplasma gondii is an obligate, intracellular, apicomplexan parasite that causes toxoplasmosis. Although the global prevalence of toxoplasmosis has been estimated to be approximately 30%, there is limited seroprevalence data in Ghana, with a dearth of information on the impact of T. gondii on haematological parameters in exposed persons. Methods: Questionnaires were administered to 300 consenting individuals to obtain demographic information and assessment of their risk of exposure to T. gondii. Using anti- T. gondii IgG/IgM combo test kits, seropositivity to parasite-specific IgG and/or IgM was determined. A haematological analyser was used to measure haematological parameters. Results: The participants included 58 males and 242 females, and ranged in age from 6 months to 84 years, with a median age of 27 years. There was an overall seroprevalence of 50.3% (n=151), with 49.7% (n=149) of the study participants seropositive for IgG and 1% (n=3) testing positive for IgM. Furthermore, the observed seroprevalence among pregnant women was 56.4% (n=62). With regards to the different communities in which the hospitals were located, a seroprevalence of 55.6% was observed in the rural community, 50.6% in the peri-urban community and 47.1% in the urban community. The study identified cat ownership, contact with cat litter [RR (95% CI: 1.76 (1.23-2.53), 1.66 (1.03-2.67), 1.25(1.00-1.57)] and age (p<0.001) as risk factors for infection. Analyses of haematological data also revealed significant differences between the red blood cell counts (p=0.038) and mean corpuscular volumes (p=0.0007) of seropositive and seronegative study participants. Conclusions: About half of the study population, including a significant number of women of reproductive age carried antibodies against T. gondii, raising questions about the risk of congenital toxoplasmosis, as well as possible links to anaemia. We, therefore, recommend that screening for Toxoplasma gondii be included in the routine screening of pregnant women seeking antenatal care.

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