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Frontiers in Immunology 2020PD-1 as an immune checkpoint molecule down-regulates T cell activity during immune responses in order to prevent autoimmune tissue damage. In chronic infections or... (Review)
Review
PD-1 as an immune checkpoint molecule down-regulates T cell activity during immune responses in order to prevent autoimmune tissue damage. In chronic infections or tumors, lasting antigen-exposure leads to permanent PD-1 expression that can limit immune-mediated clearance of pathogens or degenerated cells. Blocking PD-1 can enhance T cell function; in cancer treatment PD-1 blockade is already used as a successful therapy. However, the role of PD-1 expression and blocking in the context of acute and chronic infections is less defined. Building on its success in cancer therapy leads to the hypothesis that blocking PD-1 in infectious diseases is also beneficial in acute or chronic infections. This review will focus on the role of PD-1 expression in acute and chronic infections with virus, bacteria, and parasites, with a particular focus on recent studies regarding PD-1 blockade in infectious diseases.
Topics: Animals; Antigens, Viral; Autoantigens; Bacterial Infections; Humans; Immune Tolerance; Infections; Lymphocyte Activation; Lymphocyte Subsets; Mice, Transgenic; Polymorphism, Single Nucleotide; Programmed Cell Death 1 Receptor; Protozoan Infections; Sepsis; Virus Diseases
PubMed: 32265932
DOI: 10.3389/fimmu.2020.00487 -
Methods in Molecular Biology (Clifton,... 2021RNA helicases are proteins found in all kingdoms of life, and they are associated with all processes involving RNA from transcription to decay. They use NTP binding and... (Review)
Review
RNA helicases are proteins found in all kingdoms of life, and they are associated with all processes involving RNA from transcription to decay. They use NTP binding and hydrolysis to unwind duplexes, to remodel RNA structures and protein-RNA complexes, and to facilitate the unidirectional metabolism of biological processes. Viral, bacterial, and eukaryotic parasites have an intimate need for RNA helicases in their reproduction. Moreover, various disorders, like cancers, are often associated with a perturbation of the host's helicase activity. Thus, RNA helicases provide a rich source of targets for the development of therapeutic or prophylactic drugs. In this review, we provide an overview of the different targeting strategies against helicases, the different types of compounds explored, the proposed inhibitory mechanisms of the compounds on the proteins, and the therapeutic potential of these compounds in the treatment of various disorders.
Topics: Animals; Bacterial Infections; Cell Line; Enzyme Inhibitors; Humans; Protozoan Infections; RNA Helicases; Virus Diseases
PubMed: 33201461
DOI: 10.1007/978-1-0716-0935-4_3 -
Journal of Clinical Microbiology Jan 2024Human infections with the protozoan have been increasingly reported in the medical literature over the past three decades. Initial reports were based on microscopic... (Review)
Review
Human infections with the protozoan have been increasingly reported in the medical literature over the past three decades. Initial reports were based on microscopic identification of the purported pathogen in respiratory specimens. Later, a polymerase chain reaction (PCR) was developed to detect , following which there has been a significant increase in reports. In this minireview, we thoroughly examine the published reports of infection to evaluate its potential role as a human pathogen. We examined the published images and videos of purported compared its morphology and motility characteristics with host bronchial ciliated epithelial cells and true derived from cockroaches, analyzed the published PCR that is being used for its diagnosis, and reviewed the clinical data of patients reported in the English and Chinese literature. From our analysis, we conclude that the images and videos from human specimens do not represent true and are predominantly misidentified ciliated epithelial cells. Additionally, we note that there is insufficient clinical evidence to attribute the cases to infection, as the clinical manifestations are non-specific, possibly caused by other infections and comorbidities, and there is no associated tissue pathology attributable to . Finally, our analysis reveals that the published PCR is not specific to and can amplify DNA from commensal trichomonads. Based on this thorough review, we emphasize the need for rigorous scientific scrutiny before a microorganism is acknowledged as a novel human pathogen and discuss the potential harms of misdiagnoses for patient care and scientific literature.
Topics: Humans; Protozoan Infections; Parabasalidea; Diagnostic Errors
PubMed: 37902329
DOI: 10.1128/jcm.00845-23 -
Expert Opinion on Therapeutic Patents Mar 2023, and are the causative agents of toxoplasmosis, trichomoniasis, and giardiasis, three important infections threatening human health and affecting millions of people... (Review)
Review
INTRODUCTION
, and are the causative agents of toxoplasmosis, trichomoniasis, and giardiasis, three important infections threatening human health and affecting millions of people worldwide. Although drugs and treatment are available to fight these protozoan parasites, side effects and increasing drug resistance require continuous efforts for the development of novel effective drugs.
AREAS COVERED
The patents search was carried out in September/October 2022 with four official scientific databases (Espacenet, Scifinder, Reaxys, Google Patents). Treatments for toxoplasmosis, trichomoniasis, and giardiasis (2015-2022) have been grouped according to their chemotypes. In particular, novel chemical entities have been reported and investigated for their structure-activity relationship, when accessible. On the other hand, drug repurposing, extensively exploited to obtain novel antiprotozoal treatment, has been in-depth described. Finally, natural metabolites and extracts have also been reported.
EXPERT OPINION
, and are protozoan infections usually controlled by immune system in immunocompetent patients; however, they could represent a threatening health for immunocompromised people. The needs of novel effective drugs, endowed with new mechanisms of actions, arises from the increasing drug resistance affecting antibiotic as well as antiprotozoal therapies. In this review different therapeutic approaches to treat protozoan infections have been reported.
Topics: Humans; Giardiasis; Trichomonas vaginalis; Toxoplasma; Patents as Topic; Antiprotozoal Agents; Trichomonas Infections; Toxoplasmosis
PubMed: 37099697
DOI: 10.1080/13543776.2023.2206017 -
Frontiers in Immunology 2020Although viruses and bacteria have been known as agents of diseases since 1546, 250 years went by until the first vaccines against these pathogens were developed (1796... (Review)
Review
Although viruses and bacteria have been known as agents of diseases since 1546, 250 years went by until the first vaccines against these pathogens were developed (1796 and 1800s). In contrast, Malaria, which is a protozoan-neglected disease, has been known since the 5th century BCE and, despite 2,500 years having passed since then, no human vaccine has yet been licensed for Malaria. Additionally, no modern human vaccine is currently licensed against Visceral or Cutaneous leishmaniasis. Vaccination against Malaria evolved from the inoculation of irradiated sporozoites through the bite of Anopheles mosquitoes in 1930's, which failed to give protection, to the use of controlled human Malaria infection (CHMI) provoked by live sporozoites of and curtailed with specific chemotherapy since 1940's. Although the use of CHMI for vaccination was relatively efficacious, it has some ethical limitations and was substituted by the use of injected recombinant vaccines expressing the main antigens of the parasite cycle, starting in 1980. Pre-erythrocytic (PEV), Blood stage (BSV), transmission-blocking (TBV), antitoxic (AT), and pregnancy-associated Malaria vaccines are under development. Currently, the RTS,S-PEV vaccine, based on the circumsporozoite protein, is the only one that has arrived at the Phase III trial stage. The "R" stands for the central repeat region of circumsporozoite protein (CSP); the "T" for the T-cell epitopes of the CSP; and the "" for hepatitis B surface antigen (HBsAg). In Africa, this latter vaccine achieved only 36.7% vaccine efficacy (VE) in 5-7 years old children and was associated with an increase in clinical cases in one assay. Therefore, in spite of 35 years of research, there is no currently licensed vaccine against Malaria. In contrast, more progress has been achieved regarding prevention of leishmaniasis by vaccine, which also started with the use of live vaccines. For ethical reasons, these were substituted by second-generation subunit or recombinant DNA and protein vaccines. Currently, there is one live vaccine for humans licensed in Uzbekistan, and four licensed veterinary vaccines against visceral leishmaniasis: Leishmune® (76-80% VE) and CaniLeish® (68.4% VE), which give protection against strong endpoints (severe disease and deaths under natural conditions), and, under less severe endpoints (parasitologically and PCR-positive cases), Leishtec® developed 71.4% VE in a low infective pressure area but only 35.7% VE and transient protection in a high infective pressure area, while Letifend® promoted 72% VE. A human recombinant vaccine based on the Nucleoside hydrolase NH36 of , the main antigen of the Leishmune® vaccine, and the sterol 24-c-methyltransferase (SMT) from has reached the Phase I clinical trial phase but has not yet been licensed against the disease. This review describes the history of vaccine development and is focused on licensed formulations that have been used in preventive medicine. Special attention has been given to the delay in the development and licensing of human vaccines against Protozoan infections, which show high incidence worldwide and still remain severe threats to Public Health.
Topics: Adult; Animals; Child; Child, Preschool; Female; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Leishmania donovani; Leishmaniasis Vaccines; Leishmaniasis, Visceral; Licensure; Malaria Vaccines; Malaria, Falciparum; Mass Vaccination; Plasmodium falciparum; Pregnancy; Vaccines, Attenuated; Vaccines, Live, Unattenuated; Vaccines, Synthetic
PubMed: 32210953
DOI: 10.3389/fimmu.2020.00204 -
Acta Tropica Jul 2023Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated... (Review)
Review
Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies.
Topics: Animals; Humans; Annexins; Parasitic Diseases; Protozoan Infections; Malaria; Leishmaniasis; Parasites
PubMed: 37172709
DOI: 10.1016/j.actatropica.2023.106942 -
Journal of Clinical Lipidology 2021Although the role of the LDL receptor concerning lipids is well known, its role in various viral and parasitic infections, and in regulating the inflammatory response is... (Review)
Review
Although the role of the LDL receptor concerning lipids is well known, its role in various viral and parasitic infections, and in regulating the inflammatory response is poorly understood. Several infectious agents use the LDL receptor as a port of entry, and others depend on it for their cycle of infection. In this review, we focus on the discovery, structure, and normal function of the LDL receptor, as well as its role in a selection of infections. The LDL receptor plays an important role in certain infections and is a potential target for treatment deserving further research.
Topics: Animals; Binding Sites; Cholesterol, LDL; Hepacivirus; Humans; Lipoproteins, LDL; Mice; Protein Binding; Protozoan Infections; Receptors, LDL; Toxoplasma; Trypanosoma cruzi; Vesicular stomatitis Indiana virus; Virus Diseases
PubMed: 34645587
DOI: 10.1016/j.jacl.2021.09.048 -
Genes Aug 2019The epithelium represents the first and most extensive line of defence against pathogens, toxins and pollutant agents in humans. In general, pathogens have developed... (Review)
Review
The epithelium represents the first and most extensive line of defence against pathogens, toxins and pollutant agents in humans. In general, pathogens have developed strategies to overcome this barrier and use it as an entrance to the organism. , and spp. are amoebae mainly responsible for intestinal dysentery, meningoencephalitis and keratitis, respectively. These amoebae cause significant morbidity and mortality rates. Thus, the identification, characterization and validation of molecules participating in host-parasite interactions can provide attractive targets to timely intervene disease progress. In this work, we present a compendium of the parasite adhesins, lectins, proteases, hydrolases, kinases, and others, that participate in key pathogenic events. Special focus is made for the analysis of assorted molecules and mechanisms involved in the interaction of the parasites with epithelial surface receptors, changes in epithelial junctional markers, implications on the barrier function, among others. This review allows the assessment of initial host-pathogen interaction, to correlate it to the potential of parasite invasion.
Topics: Acanthamoeba; Animals; Entamoeba histolytica; Epithelial Cells; Host-Parasite Interactions; Humans; Naegleria fowleri; Protozoan Infections
PubMed: 31416298
DOI: 10.3390/genes10080618 -
International Journal For Parasitology Jan 2020Second and third generation sequencing methods are crucial for population genetic studies, and variant detection is a popular approach for exploiting this sequence data.... (Review)
Review
Second and third generation sequencing methods are crucial for population genetic studies, and variant detection is a popular approach for exploiting this sequence data. While mini- and microsatellites are historically useful markers for studying important Protozoa such as Toxoplasma and Plasmodium spp., detecting non-repetitive variants such as those found in genes can be fundamental to investigating a pathogen's biology. These variants, namely single nucleotide polymorphisms and insertions and deletions, can help elucidate the genetic basis of an organism's pathogenicity, identify selective pressures, and resolve phylogenetic relationships. They also have the added benefit of possessing a comparatively low mutation rate, which contributes to their stability. However, there is a plethora of variant analysis tools with nuanced pipelines and conflicting recommendations for best practise, which can be confounding. This lack of standardisation means that variant analysis requires careful parameter optimisation, an understanding of its limitations, and the availability of high quality data. This review explores the value of variant detection when applied to non-model organisms such as clinically important protozoan pathogens. The limitations of current methods are discussed, including special considerations that require the end-users' attention to ensure that the results generated are reproducible, and the biological conclusions drawn are valid.
Topics: Animals; Computational Biology; DNA, Protozoan; Drug Resistance; Genetic Variation; Genetics, Population; Genome, Protozoan; High-Throughput Nucleotide Sequencing; Humans; Leishmania; Parasites; Phylogeny; Plasmodium; Polymorphism, Single Nucleotide; Protozoan Infections; Sequence Analysis, DNA; Toxoplasma; Trypanosoma cruzi
PubMed: 31857072
DOI: 10.1016/j.ijpara.2019.10.004 -
Impact of parasitic infection on mental health and illness in humans in Africa: a systematic review.Parasitology Jul 2022A growing body of research implicates inflammation as a potential pathway in the aetiology and pathophysiology of some mental illnesses. A systematic review was...
A growing body of research implicates inflammation as a potential pathway in the aetiology and pathophysiology of some mental illnesses. A systematic review was conducted to determine the association between parasitic infection and mental illnesses in humans in Africa and reviewed the state of the evidence available. The search focused on publications from Africa documenting the relationship between parasites from two parasite groups, helminths and protozoans, and four classifications of mental illness: mood affective disorders, neurotic and stress-related disorders, schizotypal disorders and unspecified mental illnesses. In the 26 reviewed papers, the prevalence of mental illness was significantly higher in people with parasitic infection compared to those without infection, i.e., 58.2% 41.8% ( < 0.001). An overall odds ratio found that the association of having a mental illness when testing positive for a parasitic infection was four times that of people without infection. Whilst the study showed significant associations between parasite infection and mental illness, it also highlights gaps in the present literature on the pathophysiology of mental illness in people exposed to parasite infection. This study highlighted the importance of an integrated intervention for parasitic infection and mental illness.
Topics: Africa; Animals; Helminthiasis; Humans; Inflammation; Mental Disorders; Mental Health; Parasitic Diseases; Prevalence; Protozoan Infections
PubMed: 35549773
DOI: 10.1017/S0031182022000166