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JCI Insight Mar 2024Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing...
Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing evidence underscores the importance of PD-1 on macrophages for dampening immune responses. However, the mechanism governing PD-1 expression in macrophages in chronic inflammation remains largely unknown. TGF-β1 is abundant within chronic inflammatory microenvironments. Here, based on public databases, significantly positive correlations between PDCD1 and TGFB1 gene expression were observed in most human tumors. Of note, among immune infiltrates, macrophages as the predominant infiltrate expressed higher PDCD1 and TGFBR1/TGFBR2 genes. MC38 colon cancer and Schistosoma japonicum infection were used as experimental models for chronic inflammation. PD-1hi macrophages from chronic inflammatory tissues displayed an immunoregulatory pattern and expressed a higher level of TGF-β receptors. Either TGF-β1-neutralizing antibody administration or macrophage-specific Tgfbr1 knockdown largely reduced PD-1 expression on macrophages in animal models. We further demonstrated that TGF-β1 directly induced PD-1 expression on macrophages. Mechanistically, TGF-β1-induced PD-1 expression on macrophages was dependent on SMAD3 and STAT3, which formed a complex at the Pdcd1 promoter. Collectively, our study shows that macrophages adapt to chronic inflammation through TGF-β1-triggered cooperative SMAD3/STAT3 signaling that induces PD-1 expression and modulates macrophage function.
Topics: Animals; Humans; Transforming Growth Factor beta1; Receptor, Transforming Growth Factor-beta Type I; Programmed Cell Death 1 Receptor; Macrophages; Inflammation; Smad3 Protein; STAT3 Transcription Factor
PubMed: 38441961
DOI: 10.1172/jci.insight.165544 -
Clinical Microbiology Reviews Mar 2024Schistosomiasis is a neglected tropical disease caused by the helminth spp. and has the second highest global impact of all parasites. are transmitted through contact... (Review)
Review
Schistosomiasis is a neglected tropical disease caused by the helminth spp. and has the second highest global impact of all parasites. are transmitted through contact with contaminated fresh water predominantly in Africa, Asia, the Middle East, and South America. Due to the widespread prevalence of , co-infection with other infectious agents is common but often poorly described. Herein, we review recent literature describing the impact of co-infection between species and co-infection with blood-borne protozoa, soil-transmitted helminths, various intestinal protozoa, , , various urinary tract infection-causing agents, and viral pathogens. In each case, disease severity and, of particular interest, the immune landscape, are altered as a consequence of co-infection. Understanding the impact of schistosomiasis co-infections will be important when considering treatment strategies and vaccine development moving forward.
Topics: Humans; Coinfection; Schistosomiasis; Africa; Soil; Prevalence; Helminthiasis
PubMed: 38319102
DOI: 10.1128/cmr.00098-23 -
Trends in Parasitology Feb 2024The dissemination of protozoan and metazoan parasites through host tissues is hindered by cellular barriers, dense extracellular matrices, and fluid forces in the... (Review)
Review
The dissemination of protozoan and metazoan parasites through host tissues is hindered by cellular barriers, dense extracellular matrices, and fluid forces in the bloodstream. To overcome these diverse biophysical impediments, parasites implement versatile migratory strategies. Parasite-exerted mechanical forces and upregulation of the host's cellular contractile machinery are the motors for these strategies, and these are comparably better characterized for protozoa than for helminths. Using the examples of the protozoans, Toxoplasma gondii and Plasmodium, and the metazoan, Schistosoma mansoni, we highlight how quantitative tools such as traction force and reflection interference contrast microscopies have improved our understanding of how parasites alter host mechanobiology to promote their migration.
Topics: Animals; Parasites; Biomechanical Phenomena; Helminths; Toxoplasma; Plasmodium
PubMed: 38172015
DOI: 10.1016/j.pt.2023.12.001 -
Tropical Medicine and Infectious Disease Jul 2023A remarkable characteristic of infectious diseases classified as Neglected Tropical Diseases (NTDs) is the fact that they are mostly transmitted in tropical and... (Review)
Review
A remarkable characteristic of infectious diseases classified as Neglected Tropical Diseases (NTDs) is the fact that they are mostly transmitted in tropical and subtropical regions with poor conditions of sanitation and low access to healthcare, which makes transmission areas more likely to overlap. Two of the most important NTDs, schistosomiasis and leishmaniasis, despite being caused by very different etiological agents, have their pathogenesis heavily associated with immune-mediated mechanisms, and spp. and spp. have been shown to simultaneously infect humans. Still, the consequences of coinfections remain underexplored. As the inflammatory processes elicited by each one of these parasites can influence the other, several changes have been observed due to this coinfection in naturally infected humans, experimental models, and in vitro cell assays, including modifications in susceptibility to infection, pathogenesis, prognostic, and response to treatment. Herein, we review the current knowledge in coinfections in both human populations and experimental models, with special regard to how schistosomiasis affects tegumentary leishmaniasis, discuss future perspectives, and suggest a few steps to further improve our understanding in this model of parasite-host-parasite interaction.
PubMed: 37624321
DOI: 10.3390/tropicalmed8080383 -
Acta Parasitologica Dec 2023An association between Schistosoma japonicum and colorectal cancer in humans has been known since a long time; however, this association remains understudied and lacks... (Review)
Review
BACKGROUND
An association between Schistosoma japonicum and colorectal cancer in humans has been known since a long time; however, this association remains understudied and lacks comprehensive experimentation support.
OBJECTIVE
Various epidemiological and pathological studies have established the role of chronic inflammation as a major factor behind the induction of colorectal cancer. The aim of this review is to present the current knowledge on the association of Schistosoma japonicum with colorectal cancer.
RESULT
Mechanisms which lead to induction and progression of colorectal cancer are highlighted along with diagnosis and treatment for the same. Further, various methodologies, including mass drug administration, use of new drugs and vaccines, role of apoptosis, and histone-modifying enzymes, have been described which can either prevent the schistosomal infection itself or can check it from reaching an advanced stage.
CONCLUSIONS
Epidemiological, clinical, pathological and surgical studies suggest that Schistosoma japonicum is responsible for induction of colorectal cancer. However, thorough clinical studies are required to support and globally accept this notion. Further, methodologies highlighted in this work can be employed in order to take care of schistosomal infection or address the cancer induction and progression.
Topics: Animals; Humans; Schistosoma japonicum; Inflammation; Colorectal Neoplasms
PubMed: 37594685
DOI: 10.1007/s11686-023-00707-9 -
Visceral Medicine Aug 2023Despite long-term preventative efforts by local public health authorities, the prevalence of fluke infection remains high in specific areas in eastern and southeastern... (Review)
Review
BACKGROUND
Despite long-term preventative efforts by local public health authorities, the prevalence of fluke infection remains high in specific areas in eastern and southeastern Asia. Recently increasing travel or migration activities have led to the transfer and spread of such infections from endemic areas to other regions.
SUMMARY
The epidemiology, clinical signs, and symptoms for three common blood and liver flukes, namely , , and , are described in this review, and their current diagnosis and management strategy are reviewed. These flukes are considered clinically important because of the increased risk of liver or biliary cancer.
KEY MESSAGES
Early treatment and prevention of disease spread can reduce the incidence of related hepatobiliary cancer. Recognition of these fluke infection is essential for a correct diagnosis and early treatment to prevent the development of deadly cancers.
PubMed: 37901386
DOI: 10.1159/000531599 -
European Journal of Microbiology &... May 2024Schistosomiasis is a neglected tropical disease that is prevalent in low- and middle-income countries. There are five human pathogenic species, of which Schistosoma... (Review)
Review
Schistosomiasis is a neglected tropical disease that is prevalent in low- and middle-income countries. There are five human pathogenic species, of which Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum are the most prevalent worldwide and cause the greatest burden of disease in terms of mortality and morbidity. In addition, hybrid schistosomes have been identified through molecular analysis. Human infection occurs when cercariae, the larval form of the parasite, penetrate the skin of people while bathing in contaminated waters such as lakes and rivers. Schistosomiasis can cause both urogenital and intestinal symptoms. Urogenital symptoms include haematuria, bladder fibrosis, kidney damage, and an increased risk of bladder cancer. Intestinal symptoms may include abdominal pain, sometimes accompanied by diarrhoea and blood in the stool. Schistosomiasis affects more than 250 million people and causes approximately 70 million Disability-Adjusted Life Years (DALYs), mainly in Africa, South America, and Asia. To control infection, it is essential to establish sensitive and specific diagnostic tests for epidemiological surveillance and morbidity reduction. This review provides an overview of schistosomiasis, with a focus on available diagnostic tools for Schistosoma spp. Current molecular detection methods and progress in the development of new diagnostics for schistosomiasis infection are also discussed.
PubMed: 38498078
DOI: 10.1556/1886.2024.00013 -
International Journal of Molecular... Jan 2024Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. is a highly pathogenic helminth... (Review)
Review
Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.
Topics: Animals; Female; Cattle; Humans; Schistosomiasis japonica; Schistosoma japonicum; Vaccines; Schistosomiasis; Vaccination; China; Buffaloes
PubMed: 38338980
DOI: 10.3390/ijms25031707