Introduction: Live microfilariae (mf) and mf-derived extracellular vesicles (EVs) have been shown to modulate human antigen presenting cell (APC) function, most notably by suppressing the induction of IL-12 (and other pro-inflammatory cytokines) following activation with LPS and interferon-y.
Methods: To explore further how EVs alter human APC function, we studied the effect of mf and EVs on human elutriated monocyte-derived dendritic cells (DC) following exposure to Mf, mf-derived excretory/secretory (E/S) products, E/S depleted of EVs through ultracentrifugation and purified EVs. After demonstrating that the measurable responses induced by live mf could be recapitulated by EVs and EV-containing E/S, we next performed RNAseq analysis of human DC following exposure to live mf, EVs, E/S, or EV-depleted E/S.
Eosinophils, traditionally associated as central innate effector cells with type 2 immunity during allergic and helminth parasitic diseases, have recently been revealed to have important roles in tissue homeostasis as well as host defense in a broader variety of infectious diseases. In a dedicated session at the 2023 biennial conference of the International Eosinophil Society titled "Eosinophils in Host Defense," the multifaceted roles eosinophils play against diverse pathogens, ranging from parasites to fungi, bacteria, and viruses, were presented. In this review, the session speakers offer a comprehensive summary of recent discoveries across pathogen classes, positioning eosinophils as pivotal leukocytes in both host defense and pathology.
View Article and Find Full Text PDFDiarrheal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with decreases the severity of diarrhea. Here, we show that is highly prevalent in the stools of asymptomatic school-aged children.
View Article and Find Full Text PDFTo unravel the heterogeneity and molecular signature of effector memory Th2 cells (Tem2), we analyzed 23 individuals' PBMCs of filaria-infected (Filaria+) and 24 healthy volunteers (Filaria-), with or without coincident house dust mite (HDM) allergic sensitization. Flow cytometry revealed 3 CD4+ Tem subsets - CCR4+CCR6+CRTH2- Tem17, CCR4+CCR6-CRTH2+ Tem2, and CCR6+CCR4+CRTH2+ Tem17.2 - markedly enriched in Filaria+ individuals.
View Article and Find Full Text PDFOxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis.
View Article and Find Full Text PDFBackground: The immunologic mechanisms underlying pulmonary type 2 inflammation, including the dynamics of eosinophil recruitment to the lungs, still need to be elucidated.
Objective: We sought to investigate how IL-13-producing T2 effector cells trigger eosinophil migration in house dust mite (HDM)-driven allergic pulmonary inflammation.
Methods: Multiparameter and molecular profiling of murine lungs with HDM-induced allergy was investigated in the absence of IL-13 signaling by using IL-13Rα1-deficient mice and separately through adoptive transfer of CD4 T cells from IL-5-deficient mice into TCRα mice before allergic inflammation.
We generated CD4 T cell lines (TCLs) reactive to either SARS-CoV-2 spike (S) or membrane (M) proteins from unexposed naïve T cells from six healthy donor volunteers to understand in fine detail whether the S and M structural proteins have intrinsic differences in driving antigen-specific CD4 T cell responses. Having shown that each of the TCLs were antigen-specific and antigen-reactive, single cell mRNA analyses demonstrated that SARS-CoV-2 S and M proteins drive strikingly distinct molecular signatures. Whereas the S-specific CD4 T cell transcriptional signature showed a marked upregulation of CCL1, CD44, IL17RB, TNFRSF18 (GITR) and IGLC3 genes, in general their overall transcriptome signature was more similar to CD4 T cell responses induced by other viral antigens (e.
View Article and Find Full Text PDFBackground: Human ascariasis is one of the most prevalent neglected tropical diseases worldwide. The immune response during human ascariasis is characterized by Th2 polarization and a mixed Th2/Th17 response during the pathogenesis of experimental larval ascariasis. Cytokines and other pro-inflammatory mediators, such as nitric oxide (NO), are involved in helminthic infections.
View Article and Find Full Text PDFTriatoma infestans is one of the most important vectors of Trypanosoma cruzi in the Americas. While feeding, they release large amounts of saliva that will counteract the host's responses triggered at the bite site. Despite the various activities described on T.
View Article and Find Full Text PDFHigh-throughput 16S rRNA sequencing has allowed the characterization of helminth-uninfected (HU) and helminth-infected (HI) gut microbiomes, revealing distinct profiles. However, there have been no qualitative or quantitative syntheses of these studies, which show marked variation in participant age, diet, pathogen of interest, and study location. A predefined minimally biased search strategy identified 23 studies in humans.
View Article and Find Full Text PDFHuman ascariasis is the most prevalent but neglected tropical disease in the world, affecting approximately 450 million people. The initial phase of Ascaris infection is marked by larval migration from the host's organs, causing mechanical injuries followed by an intense local inflammatory response, which is characterized mainly by neutrophil and eosinophil infiltration, especially in the lungs. During the pulmonary phase, the lesions induced by larval migration and excessive immune responses contribute to tissue remodeling marked by fibrosis and lung dysfunction.
View Article and Find Full Text PDFAscaris lumbricoides and Ascaris suum are two closely related parasites that infect humans and pigs. The zoonotic potential of A. suum has been a matter of debate for decades.
View Article and Find Full Text PDFHuman ascariasis is the most common and prevalent neglected tropical disease and is estimated that ~819 million people are infected around the globe, accounting for 0.861 million years of disability-adjusted life years in 2017. Even with the existence of highly effective drugs, the constant presence of infective parasite eggs in the environment contribute to a high reinfection rate after treatment.
View Article and Find Full Text PDFThe establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice.
View Article and Find Full Text PDFThis report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local infection prevalence and intensity among school-age children.
View Article and Find Full Text PDFThe Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries.
View Article and Find Full Text PDFTissue-resident macrophages (TRMs) maintain tissue homeostasis, but they can also provide a replicative niche for intracellular pathogens such as How dermal TRMs proliferate and maintain their M2 properties even in the strong T1 environment of the infected dermis is not clear. Here, we show that, in infected mice lacking IL-4/13 from eosinophils, dermal TRMs shifted to a proinflammatory state, their numbers declined, and disease was attenuated. Intravital microscopy revealed a rapid infiltration of eosinophils followed by their tight interaction with dermal TRMs.
View Article and Find Full Text PDFIntestinal parasites cause a significant public health problem worldwide due to the associated morbidities, mainly in infected school-aged children (SAC). The strategy of large-scale deworming in SAC to control the transmission of soil-transmitted helminths (STH) has been advocated by the World Health Organization and was recently adopted in Brazil; however, the long-term effects of mass deworming on the larger parasitological profile have been less studied. After a five-year period of school-based large-scale treatment for STH using an annual single dose of albendazole in a community of Sergipe state, Brazil, a marked reduction in prevalence was observed (15.
View Article and Find Full Text PDFThis study investigates the relationship between helminth infection and allergic sensitization by assessing the influence of preexisting allergy on the outcome of helminth infections, rather than the more traditional approach in which the helminth infection precedes the onset of allergy. Here we used a murine model of house dust mite-induced (HDM-induced) allergic inflammation followed by Ascaris infection to demonstrate that allergic sensitization drives an eosinophil-rich pulmonary type 2 immune response (Th2 cells, M2 macrophages, type 2 innate lymphoid cells, IL-33, IL-4, IL-13, and mucus) that directly hinders larval development and reduces markedly the parasite burden in the lungs. This effect is dependent on the presence of eosinophils, as eosinophil-deficient mice were unable to limit parasite development or numbers.
View Article and Find Full Text PDFAm J Trop Med Hyg
September 2019
Control of schistosomiasis presently relies largely on preventive chemotherapy with praziquantel through mass drug administration (MDA) programs. The Schistosomiasis Consortium for Operational Research and Evaluation has concluded five studies in four countries (Côte d'Ivoire, Kenya, Mozambique, and Tanzania) to evaluate alternative approaches to MDA. Studies involved four intervention years, with final evaluation in the fifth year.
View Article and Find Full Text PDFActa Trop
September 2019
The Kato-Katz (KK) technique is the mainstay mapping tool for the diagnosis of Schistosoma mansoni infection, despite showing poor sensitivity in cases of low-intensity infections. As an alternative, a rapid point-of-care circulating cathodic antigen diagnostic test (POC-CCA) has been commercially developed that involves a simple urine assay to detect S. mansoni, rather than a stool-based parasitological examination.
View Article and Find Full Text PDFIntroduction: Malaria transmission blocking vaccines (TBV) are innovative approaches that aim to induce immunity in humans against Plasmodium during mosquito stage, neutralizing the capacity of the infected vectors to transmit malaria. Pfs230D1-EPA/Alhydrogel®, a promising protein-protein conjugate malaria TBV, is currently being tested in human clinical trials in areas where P. falciparum malaria is coendemic with helminth parasites.
View Article and Find Full Text PDFHuman ascariasis has a global and cosmopolitan distribution, and has been characterized as the most prevalent neglected tropical disease worldwide. The development of a preventive vaccine is highly desirable to complement current measures required for this parasitic infection control and to reduce chronic childhood morbidities. In the present study, we describe the mechanism of protection elicited by a preventive vaccine against ascariasis.
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