scholarly journals The esophageal gland mediates host immune evasion by the human parasiteSchistosoma mansoni

2020 ◽  
Vol 117 (32) ◽  
pp. 19299-19309
Author(s):  
Jayhun Lee ◽  
Tracy Chong ◽  
Phillip A. Newmark
Keyword(s):  
Stem Cells ◽  
Life Cycle ◽  
Immune Evasion ◽  
Blood Feeding ◽  
Life Cycle Stage ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Immunodeficient Mice ◽  
Immune Evasion Mechanism ◽  
Esophageal Gland

Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease affecting over 200 million people. Schistosomes develop multiple body plans while navigating their complex life cycle, which involves two different hosts: a mammalian definitive host and a molluscan intermediate host. Their survival and propagation depend upon proliferation and differentiation of stem cells necessary for parasite homeostasis and reproduction. Infective larvae released from snails carry a handful of stem cells that serve as the likely source of new tissues as the parasite adapts to life inside the mammalian host; however, the role of these stem cells during this critical life cycle stage remains unclear. Here, we characterize stem cell fates during early intramammalian development. Surprisingly, we find that the esophageal gland, an accessory organ of the digestive tract, develops before the rest of the digestive system is formed and blood feeding is initiated, suggesting a role in processes beyond nutrient uptake. To explore such a role, we examine schistosomes that lack the esophageal gland due to knockdown of a forkhead-box transcription factor,Sm-foxA, which blocks development and maintenance of the esophageal gland, without affecting the development of other somatic tissues. Intriguingly, schistosomes lacking the esophageal gland die after transplantation into naive mice, but survive in immunodeficient mice lacking B cells. We show that parasites lacking the esophageal gland are unable to lyse ingested immune cells within the esophagus before passing them into the gut. These results unveil an immune-evasion mechanism mediated by the esophageal gland, which is essential for schistosome survival and pathogenesis.

scholarly journals Metamorphoses of malaria: the role of autophagy in parasite differentiation

2011 ◽  
Vol 51 ◽  
pp. 127-136 ◽  
Author(s):  
Isabelle Coppens
Keyword(s):  
Life Cycle ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Protozoan Parasites ◽  
Membrane Complex ◽  
Autophagic Process ◽  
Inner Membrane Complex ◽  
Form Development ◽  
High Degree

Several protozoan parasites undergo a complex life cycle that alternates between an invertebrate vector and a vertebrate host. Adaptations to these different environments by the parasites are achieved by drastic changes in their morphology and metabolism. The malaria parasites must be transmitted to a mammal from a mosquito as part of their life cycle. Upon entering the mammalian host, extracellular malaria sporozoites reach the liver and invade hepatocytes, wherein they meet the challenge of becoming replication-competent schizonts. During the process of conversion, the sporozoite selectively discards organelles that are unnecessary for the parasite growth in liver cells. Among the organelles that are cleared from the sporozoite are the micronemes, abundant secretory vesicles that facilitate the adhesion of the parasite to hepatocytes. Organelles specialized in sporozoite motility and structure, such as the inner membrane complex (a major component of the motile parasite's cytoskeleton), are also eliminated from converting parasites. The high degree of sophistication of the metamorphosis that occurs at the onset of the liver-form development cascade suggests that the observed changes must be multifactorial. Among the mechanisms implicated in the elimination of sporozoite organelles, the degradative process called autophagy contributes to the remodelling of the parasite interior and the production of replicative liver forms. In a broader context, the importance of the role played by autophagy during the differentiation of protozoan parasites that cycle between insects and vertebrates is nowadays clearly emerging. An exciting prospect derived from these observations is that the parasite proteins involved in the autophagic process may represent new targets for drug development.

scholarly journals Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei.

1995 ◽  
Vol 15 (11) ◽  
pp. 5945-5956 ◽  
Author(s):  
S V Graham ◽  
J D Barry
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Life Cycle ◽  
Life Cycle Stage ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Mammalian Host ◽  
Dependent Manner ◽  
African Trypanosomes ◽  
Specific Subset

In antigenic variation in African trypanosomes, switching of the variant surface glycoprotein (VSG) allows evasion of the mammalian host immune response. Trypanosomes first express the VSG in the tsetse fly vector, at the metacyclic stage, in preparation for transfer into the mammal. In this life cycle stage, a small, specific subset (1 to 2%) of VSGs are activated, and we have shown previously that the system of activation and expression of metacyclic VSG (M-VSG) genes is very different from that used for bloodstream VSG genes (S.V. Graham, K.R. Matthews, P.G. Shiels, and J.D. Barry, Parasitology 101:361-367, 1990). Now we show that unlike other trypanosome genes including bloodstream VSG genes, M-VSG genes are expressed from promoters subject to exclusively transcriptional regulation in a life cycle stage-dependent manner. We have located an M-VSG gene promoter, and we demonstrate that it is specifically up-regulated at the metacyclic stage. This is the first demonstration of gene expression being regulated entirely at the level of transcription among the Kinetoplastida; all other protein-coding genes examined in these organisms are, at least partly, under posttranscriptional control. The distinctive mode of expression of M-VSG genes may be due to a stochastic mechanism for metacyclic VSG activation.

scholarly journals Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis in Trypanosoma cruzi

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1628
Author(s):  
Rodolpho Ornitz Oliveira Souza ◽  
Marcell Crispim ◽  
Ariel Mariano Silber ◽  
Flávia Silva Damasceno
Keyword(s):  
Cell Proliferation ◽  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Host Cells ◽  
Glutamine Metabolism ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Developmental Cycle ◽  
Parasite Life Cycle

Trypanosoma cruzi is the aetiologic agent of Chagas disease, which affects people in the Americas and worldwide. The parasite has a complex life cycle that alternates among mammalian hosts and insect vectors. During its life cycle, T. cruzi passes through different environments and faces nutrient shortages. It has been established that amino acids, such as proline, histidine, alanine, and glutamate, are crucial to T. cruzi survival. Recently, we described that T. cruzi can biosynthesize glutamine from glutamate and/or obtain it from the extracellular environment, and the role of glutamine in energetic metabolism and metacyclogenesis was demonstrated. In this study, we analysed the effect of glutamine analogues on the parasite life cycle. Here, we show that glutamine analogues impair cell proliferation, the developmental cycle during the infection of mammalian host cells and metacyclogenesis. Taken together, these results show that glutamine is an important metabolite for T. cruzi survival and suggest that glutamine analogues can be used as scaffolds for the development of new trypanocidal drugs. These data also reinforce the supposition that glutamine metabolism is an unexplored possible therapeutic target.

scholarly journals Activity of a Trypanosome Metacyclic Variant Surface Glycoprotein Gene Promoter Is Dependent upon Life Cycle Stage and Chromosomal Context

1998 ◽  
Vol 18 (3) ◽  
pp. 1137-1146 ◽  
Author(s):  
Sheila V. Graham ◽  
Ben Wymer ◽  
J. David Barry
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Gene Promoter ◽  
Life Cycle Stage ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Mammalian Host ◽  
African Trypanosomes ◽  
Highly Active ◽  
Internal Position

ABSTRACT African trypanosomes evade the mammalian host immune response by antigenic variation, the continual switching of their variant surface glycoprotein (VSG) coat. VSG is first expressed at the metacyclic stage in the tsetse fly as a preadaptation to life in the mammalian bloodstream. In the metacyclic stage, a specific subset (<28; 1 to 2%) of VSG genes, located at the telomeres of the largest trypanosome chromosomes, are activated by a system very different from that used for bloodstream VSG genes. Previously we showed that a metacyclic VSG (M-VSG) gene promoter was subject to life cycle stage-specific control of transcription initiation, a situation unique in Kinetoplastida, where all other genes are regulated, at least partly, posttranscriptionally (S. V. Graham and J. D. Barry, Mol. Cell. Biol. 15:5945–5956, 1985). However, while nuclear run-on analysis had shown that the ILTat 1.22 M-VSG gene promoter was transcriptionally silent in bloodstream trypanosomes, it was highly active when tested in bloodstream-form transient transfection. Reasoning that chromosomal context may contribute to repression of M-VSG gene expression, here we have integrated the 1.22 promoter, linked to a chloramphenicol acetyltransferase (CAT) reporter gene, back into its endogenous telomere or into a chromosomal internal position, the nontranscribed spacer region of ribosomal DNA, in both bloodstream and procyclic trypanosomes. Northern blot analysis and CAT activity assays show that in the bloodstream, the promoter is transcriptionally inactive at the telomere but highly active at the chromosome-internal position. In contrast, it is inactive in both locations in procyclic trypanosomes. Both promoter sequence and chromosomal location are implicated in life cycle stage-specific transcriptional regulation of M-VSG gene expression.

scholarly journals Stem cell heterogeneity drives the parasitic life cycle of Schistosoma mansoni

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Bo Wang ◽  
Jayhun Lee ◽  
Pengyang Li ◽  
Amir Saberi ◽  
Huiying Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Life Cycle ◽  
Schistosoma Mansoni ◽  
Sexual Reproduction ◽  
Adult Stem Cells ◽  
Developmental Plasticity ◽  
Mammalian Host ◽  
Cell Heterogeneity ◽  
Life Cycle Stages

Schistosomes are parasitic flatworms infecting hundreds of millions of people. These parasites alternate between asexual reproduction in molluscan hosts and sexual reproduction in mammalian hosts; short-lived, water-borne stages infect each host. Thriving in such disparate environments requires remarkable developmental plasticity, manifested by five body plans deployed throughout the parasite’s life cycle. Stem cells in Schistosoma mansoni provide a potential source for such plasticity; however, the relationship between stem cells from different life-cycle stages remains unclear, as does the origin of the germline, required for sexual reproduction. Here, we show that subsets of larvally derived stem cells are likely sources of adult stem cells and the germline. We also identify a novel gene that serves as the earliest marker for the schistosome germline, which emerges inside the mammalian host and is ultimately responsible for disease pathology. This work reveals the stem cell heterogeneity driving the propagation of the schistosome life cycle.

Ultrastructural analysis of “Sensory” surface nerve endings and “putative” neurotransmitter sites in Schistosoma mansoni Miracidia

1989 ◽  
Vol 47 ◽  
pp. 962-963
Author(s):  
Betty Ruth Jones ◽  
Steve Chi-Tang Pan
Keyword(s):  
Nervous System ◽  
Life Cycle ◽  
Schistosoma Mansoni ◽  
Snail Host ◽  
Complex Life Cycle ◽  
Rational Approach ◽  
Effective Control ◽  
The Social ◽  
Social And Economic Development ◽  
Basic Biology

INTRODUCTION: Schistosomiasis has been described as “one of the most devastating diseases of mankind, second only to malaria in its deleterious effects on the social and economic development of populations in many warm areas of the world.” The disease is worldwide and is probably spreading faster and becoming more intense than the overall research efforts designed to provide the basis for countering it. Moreover, there are indications that the development of water resources and the demands for increasing cultivation and food in developing countries may prevent adequate control of the disease and thus the number of infections are increasing.Our knowledge of the basic biology of the parasites causing the disease is far from adequate. Such knowledge is essential if we are to develop a rational approach to the effective control of human schistosomiasis. The miracidium is the first infective stage in the complex life cycle of schistosomes. The future of the entire life cycle depends on the capacity and ability of this organism to locate and enter a suitable snail host for further development, Little is known about the nervous system of the miracidium of Schistosoma mansoni and of other trematodes. Studies indicate that miracidia contain a well developed and complex nervous system that may aid the larvae in locating and entering a susceptible snail host (Wilson, 1970; Brooker, 1972; Chernin, 1974; Pan, 1980; Mehlhorn, 1988; and Jones, 1987-1988).

scholarly journals Metabolic reprogramming during the Trypanosoma brucei life cycle

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 683 ◽  
Author(s):  
Terry K. Smith ◽  
Frédéric Bringaud ◽  
Derek P. Nolan ◽  
Luisa M. Figueiredo
Keyword(s):  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Model Organism ◽  
Protozoan Parasite ◽  
Tsetse Fly ◽  
Metabolic Reprogramming ◽  
Mammalian Host ◽  
Insect Vector ◽  
Environmental Signals ◽  
Cellular Metabolic Activity

Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

scholarly journals DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashton C. Trotman-Grant ◽  
Mahmood Mohtashami ◽  
Joshua De Sousa Casal ◽  
Elisa C. Martinez ◽  
Dylan Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Stromal Cell ◽  
Hematopoietic Stem ◽  
Free System ◽  
Cell Therapies ◽  
Immunodeficient Mice ◽  
Human T Cell

AbstractT cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the field is the development of a clinically relevant system that is readily scalable to generate large numbers of T-lineage cells from hematopoietic stem/progenitor cells (HSPCs). Here, we report a stromal cell-free, microbead-based approach that supports the efficient in vitro development of both human progenitor T (proT) cells and T-lineage cells from CD34+cells sourced from cord blood, GCSF-mobilized peripheral blood, and pluripotent stem cells (PSCs). DL4-μbeads, along with lymphopoietic cytokines, induce an ordered sequence of differentiation from CD34+ cells to CD34+CD7+CD5+ proT cells to CD3+αβ T cells. Single-cell RNA sequencing of human PSC-derived proT cells reveals a transcriptional profile similar to the earliest thymocytes found in the embryonic and fetal thymus. Furthermore, the adoptive transfer of CD34+CD7+ proT cells into immunodeficient mice demonstrates efficient thymic engraftment and functional maturation of peripheral T cells. DL4-μbeads provide a simple and robust platform to both study human T cell development and facilitate the development of engineered T cell therapies from renewable sources.

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