scholarly journals Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms that Ensure Survival in Plain Sight of the Adaptive Immune System

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 679
Author(s):  
Stefan Magez ◽  
Joar Esteban Pinto Torres ◽  
Seoyeon Oh ◽  
Magdalena Radwanska
Keyword(s):  
Immune System ◽  
Trypanosoma Brucei ◽  
Adaptive Immune System ◽  
Sub Saharan Africa ◽  
Survival Strategies ◽  
Mechanical Transmission ◽  
Sub Saharan ◽  
Animal Trypanosomiasis ◽  
Host Parasite ◽  
Treatment And Diagnosis

Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing human African trypanosomiasis (HAT—sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal trypanosomiasis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Saharan Africa. Through mechanical transmission, T. vivax has also been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical human trypanosomiasis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasites, but the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies that allow trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well as the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.

scholarly journals Salivarian Trypanosomosis Have Adopted Intricate Host-Pathogen Interaction Mechanisms That Ensures Survival Plain Sight of the Adaptive Immune System

2021 ◽  
Author(s):  
Stefan Magez ◽  
Joar Esteban Pinto Torres ◽  
Seoyeon Oh ◽  
Magdalena Radwanska
Keyword(s):  
Immune System ◽  
Trypanosoma Brucei ◽  
Adaptive Immune System ◽  
Survival Strategies ◽  
Mechanical Transmission ◽  
Trypanosoma Brucei Rhodesiense ◽  
New Developments ◽  
Adaptive Immune ◽  
Host Parasite ◽  
Treatment And Diagnosis

Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing Human African Trypanosomosis (HAT - sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal Trypanosomosis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Sahara Africa. Trough mechanical transmission, T. vivax has however been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical Human Trypanosomosis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasite, but this is the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies allowing trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.

Antioxidants promote establishment of trypanosome infections in tsetse

Parasitology ◽  
2007 ◽  
Vol 134 (6) ◽  
pp. 827-831 ◽  
Author(s):  
E. T. MacLEOD ◽  
I. MAUDLIN ◽  
A. C. DARBY ◽  
S. C. WELBURN
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Trypanosoma Brucei ◽  
Sub Saharan Africa ◽  
Tsetse Flies ◽  
Oxygen Species ◽  
Infection Rates ◽  
Trypanosoma Brucei Brucei ◽  
Sub Saharan ◽  
Cyclical Transmission

SUMMARYEfficient, cyclical transmission of trypanosomes through tsetse flies is central to maintenance of human sleeping sickness and nagana across sub-Saharan Africa. Infection rates in tsetse are normally very low as most parasites ingested with the fly bloodmeal die in the fly gut, displaying the characteristics of apoptotic cells. Here we show that a range of antioxidants (glutathione, cysteine, N-acetyl-cysteine, ascorbic acid and uric acid), when added to the insect bloodmeal, can dramatically inhibit cell death of Trypanosoma brucei brucei in tsetse. Both L- and D-cysteine invoked similar effects suggesting that inhibition of trypanosome death is not dependent on protein synthesis. The present work suggests that antioxidants reduce the midgut environment protecting trypanosomes from cell death induced by reactive oxygen species.

Proteomics and theTrypanosoma bruceicytoskeleton: advances and opportunities

Parasitology ◽  
2012 ◽  
Vol 139 (9) ◽  
pp. 1168-1177 ◽  
Author(s):  
NEIL PORTMAN ◽  
KEITH GULL
Keyword(s):  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Molecular Composition ◽  
Etiological Agent ◽  
Sub Saharan Africa ◽  
Parasitic Disease ◽  
Cell Cycles ◽  
Sub Saharan ◽  
High Level

SUMMARYTrypanosoma bruceiis the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.

scholarly journals Cryptococcal Interactions with the Host Immune System

2010 ◽  
Vol 9 (6) ◽  
pp. 835-846 ◽  
Author(s):  
Kerstin Voelz ◽  
Robin C. May
Keyword(s):  
Immune System ◽  
Defense Mechanisms ◽  
Clinical Intervention ◽  
Sub Saharan Africa ◽  
Host Immune System ◽  
Opportunistic Pathogens ◽  
Content Type ◽  
Aids Pandemic ◽  
Immune Deficiencies ◽  
Sub Saharan

ABSTRACT Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment.

scholarly journals One day is enough: rapid and specific host–parasite interactions in a stickleback-trematode system

2006 ◽  
Vol 2 (3) ◽  
pp. 382-384 ◽  
Author(s):  
Gisep Rauch ◽  
Martin Kalbe ◽  
Thorsten B.H Reusch
Keyword(s):  
Immune System ◽  
Genotypic Variation ◽  
Adaptive Immune System ◽  
Host Defence ◽  
Defence Mechanism ◽  
Fish Family ◽  
Adaptive Immune ◽  
Specific Host ◽  
Host Parasite Interactions ◽  
Host Parasite

Red Queen models of host–parasite coevolution are based on genotype by genotype host–parasite interactions. Such interactions require a genotype specific host defence and, simultaneously, a genotype specific parasite infectivity. Specificity is defined here as defence or infection ability successful against only a subset of genotypes of the same species. A specific defence depends on detectable genotypic variation on the parasite side and on a host defence mechanism that differentiates between parasite genotypes. In vertebrates, the MHC-based adaptive immune system can provide such a defence mechanism, but it needs at least several days to get fully mounted. In contrast, the innate immune system is immediately ready. The trematode parasite species used here reaches the immunologically protected eye lens of its three-spined stickleback ( Gasterosteus aculeatus ) host within 24 h. Thus, it disappears too fast for the fully mounted MHC-based adaptive immune system. In a complete cross-infection experiment using five fish-families and five parasite-clones, we found for the first time fish-family by parasite-clone interactions in vertebrates, although the parasite was only exposed to the immune system for maximally one day. Such interactions require a fast genotype specific defence, suggesting the importance of other defence mechanisms than the too slow, fully mounted adaptive immune system in vertebrates.

scholarly journals Mechanisms of Arsenical and Diamidine Uptake and Resistance in Trypanosoma brucei

2003 ◽  
Vol 2 (5) ◽  
pp. 1003-1008 ◽  
Author(s):  
Enock Matovu ◽  
Mhairi L. Stewart ◽  
Federico Geiser ◽  
Reto Brun ◽  
Pascal Mäser ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Drug Sensitivity ◽  
Sleeping Sickness ◽  
Drug Uptake ◽  
Sub Saharan Africa ◽  
Parental Line ◽  
Adenosine Transport ◽  
Sub Saharan ◽  
High Level

ABSTRACT Sleeping sickness, caused by Trypanosoma brucei spp., has become resurgent in sub-Saharan Africa. Moreover, there is an alarming increase in treatment failures with melarsoprol, the principal agent used against late-stage sleeping sickness. In T. brucei, the uptake of melarsoprol as well as diamidines is thought to be mediated by the P2 aminopurine transporter, and loss of P2 function has been implicated in resistance to these agents. The trypanosomal gene TbAT1 has been found to encode a P2-type transporter when expressed in yeast. Here we investigate the role of TbAT1 in drug uptake and drug resistance in T. brucei by genetic knockout of TbAT1. Tbat1-null trypanosomes were deficient in P2-type adenosine transport and lacked adenosine-sensitive transport of pentamidine and melaminophenyl arsenicals. However, the null mutants were only slightly resistant to melaminophenyl arsenicals and pentamidine, while resistance to other diamidines such as diminazene was more pronounced. Nevertheless, the reduction in drug sensitivity might be of clinical significance, since mice infected with tbat1-null trypanosomes could not be cured with 2 mg of melarsoprol/kg of body weight for four consecutive days, whereas mice infected with the parental line were all cured by using this protocol. Two additional pentamidine transporters, HAPT1 and LAPT1, were still present in the null mutant, and evidence is presented that HAPT1 may be responsible for the residual uptake of melaminophenyl arsenicals. High-level arsenical resistance therefore appears to involve the loss of more than one transporter.

scholarly journals Novel protein candidates for serodiagnosis of African animal trypanosomosis: Evaluation of the diagnostic potential of lysophospholipase and glycerol kinase from Trypanosoma brucei

2021 ◽  
Vol 15 (12) ◽  
pp. e0009985
Author(s):  
Magamba Tounkara ◽  
Alain Boulangé ◽  
Magali Thonnus ◽  
Frédéric Bringaud ◽  
Adrien Marie Gaston Bélem ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Sub Saharan Africa ◽  
Tsetse Flies ◽  
African Countries ◽  
Human Form ◽  
Novel Proteins ◽  
Diagnostic Potential ◽  
Sub Saharan ◽  
Better Than ◽  
Novel Protein

African trypanosomosis, a parasitic disease caused by protozoan parasites transmitted by tsetse flies, affects both humans and animals in sub-Saharan Africa. While the human form (HAT) is now limited to foci, the animal form (AAT) is widespread and affects the majority of sub-Saharan African countries, and constitutes a real obstacle to the development of animal breeding. The control of AAT is hampered by a lack of standardized and easy-to used diagnosis tools. This study aimed to evaluate the diagnostic potential of TbLysoPLA and TbGK proteins from Trypanosoma brucei brucei for AAT serodiagnosis in indirect ELISA using experimental and field sera, individually, in combination, and associated with the BiP C-terminal domain (C25) from T. congolense. These novel proteins were characterized in silico, and their sequence analysis showed strong identities with their orthologs in other trypanosomes (more than 60% for TbLysoPLA and more than 82% for TbGK). TbLysoPLA displays a low homology with cattle (<35%) and Piroplasma (<15%). However, TbGK shares more than 58% with cattle and between 45–55% with Piroplasma. We could identify seven predicted epitopes on TbLysoPLA sequence and 14 potential epitopes on TbGK. Both proteins were recombinantly expressed in Escherichia coli. Their diagnostic potential was evaluated by ELISA with sera from cattle experimentally infected with T. congolense and with T.b. brucei, sera from cattle naturally infected with T. congolense, T. vivax and T.b. brucei. Both proteins used separately had poor diagnostic performance. However, used together with the BiP protein, they showed 60% of sensitivity and between 87–96% of specificity, comparable to reference ELISA tests. In conclusion, we showed that the performance of the protein combinations is much better than the proteins tested individually for the diagnosis of AAT.

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