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Nature Communications Jan 2023The ubiquitous pathogen Toxoplasma gondii has a complex lifestyle with different metabolic activities at different stages that are intimately linked to the parasitic...
The ubiquitous pathogen Toxoplasma gondii has a complex lifestyle with different metabolic activities at different stages that are intimately linked to the parasitic environments. Here we identified the eukaryotic regulator of cellular homeostasis AMP-activated protein kinase (AMPK) in Toxoplasma and discovered its role in metabolic programming during parasite's lytic cycle. The catalytic subunit AMPKα is quickly phosphorylated after the release of intracellular parasites to extracellular environments, driving energy-producing catabolism to power parasite motility and invasion into host cells. Once inside host cells, AMPKα phosphorylation is reduced to basal level to promote a balance between energy production and biomass synthesis, allowing robust parasite replication. AMPKγ depletion abolishes AMPKα phosphorylation and suppresses parasite growth, which can be partially rescued by overexpressing wildtype AMPKα but not the phosphorylation mutants. Thus, through the cyclic reprogramming by AMPK, the parasites' metabolic needs at each stage are satisfied and the lytic cycle progresses robustly.
Topics: Animals; Toxoplasma; AMP-Activated Protein Kinases; Parasites; Phosphorylation; Homeostasis
PubMed: 36702847
DOI: 10.1038/s41467-023-36084-0 -
Frontiers in Immunology 2019Protozoan parasites represent a major threat to health and contribute significantly to morbidity and mortality worldwide, especially in developing countries. This is... (Review)
Review
Protozoan parasites represent a major threat to health and contribute significantly to morbidity and mortality worldwide, especially in developing countries. This is further compounded by lack of effective vaccines, drug resistance and toxicity associated with current therapies. Multiple protozoans, including , and produce homologs of the cytokine MIF. These parasite MIF homologs are capable of altering the host immune response during infection, and play a role in immune evasion, invasion and pathogenesis. This minireview outlines well-established and emerging literature on the role of parasite MIF homologs in disease, and their potential as targets for therapeutic and preventive interventions.
Topics: Animals; Humans; Immune Evasion; Macrophage Migration-Inhibitory Factors; Parasites
PubMed: 31497025
DOI: 10.3389/fimmu.2019.01995 -
Nature Reviews. Microbiology Oct 2021Virtually all plants and animals, including humans, are home to symbiotic microorganisms. Symbiotic interactions can be neutral, harmful or have beneficial effects on... (Review)
Review
Virtually all plants and animals, including humans, are home to symbiotic microorganisms. Symbiotic interactions can be neutral, harmful or have beneficial effects on the host organism. However, growing evidence suggests that microbial symbionts can evolve rapidly, resulting in drastic transitions along the parasite-mutualist continuum. In this Review, we integrate theoretical and empirical findings to discuss the mechanisms underpinning these evolutionary shifts, as well as the ecological drivers and why some host-microorganism interactions may be stuck at the end of the continuum. In addition to having biomedical consequences, understanding the dynamic life of microorganisms reveals how symbioses can shape an organism's biology and the entire community, particularly in a changing world.
Topics: Animals; Bacteria; Evolution, Molecular; Host-Parasite Interactions; Humans; Mice; Parasites; Symbiosis
PubMed: 33875863
DOI: 10.1038/s41579-021-00550-7 -
Trends in Parasitology Jun 2023Malaria is a febrile illness caused by species of the protozoan parasite Plasmodium and is characterized by recursive infections of erythrocytes, leading to clinical... (Review)
Review
Malaria is a febrile illness caused by species of the protozoan parasite Plasmodium and is characterized by recursive infections of erythrocytes, leading to clinical symptoms and pathology. In mammals, Plasmodium parasites undergo a compulsory intrahepatic development stage before infecting erythrocytes. Liver-stage parasites have a metabolic configuration to facilitate the replication of several thousand daughter parasites. Their metabolism is of interest to identify cellular pathways essential for liver infection, to kill the parasite before onset of the disease. In this review, we summarize the current knowledge on nutrient acquisition and biosynthesis by liver-stage parasites mostly generated in murine malaria models, gaps in knowledge, and challenges to create a holistic view of the development and deficiencies in this field.
Topics: Animals; Mice; Plasmodium; Liver; Malaria; Parasites; Erythrocytes; Protozoan Proteins; Mammals
PubMed: 37061442
DOI: 10.1016/j.pt.2023.03.013 -
Frontiers in Cellular and Infection... 2023
Topics: Animals; Humans; Systems Biology; Parasitic Diseases; Parasites
PubMed: 37124048
DOI: 10.3389/fcimb.2023.1192732 -
Annual Review of Immunology Apr 2021Coevolutionary adaptation between humans and helminths has developed a finely tuned balance between host immunity and chronic parasitism due to immunoregulation. Given... (Review)
Review
Coevolutionary adaptation between humans and helminths has developed a finely tuned balance between host immunity and chronic parasitism due to immunoregulation. Given that these reciprocal forces drive selection, experimental models of helminth infection are ideally suited for discovering how host protective immune responses adapt to the unique tissue niches inhabited by these large metazoan parasites. This review highlights the key discoveries in the immunology of helminth infection made over the last decade, from innate lymphoid cells to the emerging importance of neuroimmune connections. A particular emphasis is placed on the emerging areas within helminth immunology where the most growth is possible, including the advent of genetic manipulation of parasites to study immunology and the use of engineered T cells for therapeutic options. Lastly,we cover the status of human challenge trials with helminths as treatment for autoimmune disease, which taken together, stand to keep the study of parasitic worms at the forefront of immunology for years to come.
Topics: Animals; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Immunity, Innate; Lymphocytes; Parasites; T-Lymphocytes
PubMed: 33646858
DOI: 10.1146/annurev-immunol-093019-122827 -
Frontiers in Cellular and Infection... 2023
Topics: Animals; Humans; Leishmania; Parasites; Leishmaniasis; Insect Vectors; Symbiosis
PubMed: 36949811
DOI: 10.3389/fcimb.2023.1171962 -
Journal of Theoretical Biology Oct 2021Although mortality increases with age in most organisms, senescence is missing from models of parasite evolution. Since virulence evolves according to the host's...
Although mortality increases with age in most organisms, senescence is missing from models of parasite evolution. Since virulence evolves according to the host's mortality, and since virulence influences the intensity of transmission, which determines the average age at infection and thus the mortality rate of a senescing host, we expected that epi-evolutionary feedbacks would underlie the evolution of virulence in a population of senescing hosts. We tested this idea by extending an age-structured model of epidemiological dynamics with the parasite's evolution. A straightforward prediction of our model is that stronger senescence forces the evolution of higher virulence. However, the model also reveals that the evolved virulence depends on the average age at infection, giving an evolutionary feedback with the epidemiological situation, a prediction not found when assuming a constant mortality rate with age. Additionally, and in contrast to most models of parasite evolution, we found that the virulence at the evolutionary equilibrium is influenced by whether the force of infection depends on the density or on the frequency of infected hosts, due to changes in the average age at infection. Our findings suggest that ignoring age-specific effects, and in particular senescence, can give misleading predictions about parasite evolution.
Topics: Animals; Biological Evolution; Host-Parasite Interactions; Models, Biological; Parasites; Virulence
PubMed: 33915143
DOI: 10.1016/j.jtbi.2021.110732 -
PLoS Neglected Tropical Diseases Aug 2021Protozoan parasites are responsible for severe disease and suffering in humans worldwide. Apart from disease transmission via insect vectors and contaminated soil, food,... (Review)
Review
Protozoan parasites are responsible for severe disease and suffering in humans worldwide. Apart from disease transmission via insect vectors and contaminated soil, food, or water, transmission may occur congenitally or by way of blood transfusion and organ transplantation. Several recent outbreaks associated with fresh produce and potable water emphasize the need for vigilance and monitoring of protozoan parasites that cause severe disease in humans globally. Apart from the tropical parasite Plasmodium spp., other protozoa causing debilitating and fatal diseases such as Trypanosoma spp. and Naegleria fowleri need to be studied in more detail. Climate change and socioeconomic issues such as migration continue to be major drivers for the spread of these neglected tropical diseases beyond endemic zones. Due to the complex life cycles of protozoa involving multiple hosts, vectors, and stringent growth conditions, studying these parasites has been challenging. While in vivo models may provide insights into host-parasite interaction, the ethical aspects of laboratory animal use and the challenge of ready availability of parasite life stages underline the need for in vitro models as valid alternatives for culturing and maintaining protozoan parasites. To our knowledge, this review is the first of its kind to highlight available in vitro models for protozoa causing highly infectious diseases. In recent years, several research efforts using new technologies such as 3D organoid and spheroid systems for protozoan parasites have been introduced that provide valuable tools to advance complex culturing models and offer new opportunities toward the advancement of parasite in vitro studies. In vitro models aid scientists and healthcare providers in gaining insights into parasite infection biology, ultimately enabling the use of novel strategies for preventing and treating these diseases.
Topics: Animals; Host-Parasite Interactions; Humans; Life Cycle Stages; Parasitic Diseases; Parasitology; Plasmodium; Trypanosoma
PubMed: 34437538
DOI: 10.1371/journal.pntd.0009668 -
The Journal of Animal Ecology Oct 2022Parasitism is expected to change in a warmer future, but whether warming leads to substantial increases in parasitism remains unclear. Understanding how warming effects... (Review)
Review
Parasitism is expected to change in a warmer future, but whether warming leads to substantial increases in parasitism remains unclear. Understanding how warming effects on parasitism in individual hosts (e.g. parasite load) translate to effects on population-level parasitism (e.g. prevalence, R ) remains a major knowledge gap. We conducted a literature review and identified 24 host-parasite systems that had information on the temperature dependence of parasitism at both individual host and host population levels: 13 vector-borne systems and 11 environmentally transmitted systems. We found a strong positive correlation between the thermal optima of individual- and population-level parasitism, although several of the environmentally transmitted systems exhibited thermal optima >5°C apart between individual and population levels. Parasitism thermal optima were close to vector performance thermal optima in vector-borne systems but not hosts in environmentally transmitted systems, suggesting these thermal mismatches may be more common in certain types of host-parasite systems. We also adapted and simulated simple models for both types of transmission modes and found the same pattern across the two modes: thermal optima were more strongly correlated across scales when there were more traits linking individual- to population-level processes. Generally, our results suggest that information on the temperature dependence, and specifically the thermal optimum, at either the individual or population level should provide a useful-although not quantitatively exact-baseline for predicting temperature dependence at the other level, especially in vector-borne parasite systems. Environmentally transmitted parasitism may operate by a different set of rules, in which temperature dependence is decoupled in some systems, requiring the need for trait-based studies of temperature dependence at individual and population levels.
Topics: Animals; Host-Parasite Interactions; Parasites; Symbiosis; Temperature
PubMed: 35900837
DOI: 10.1111/1365-2656.13786