RESUMO
The protozoan parasites Plasmodium, Leishmania, and Trypanosoma are transmitted by hematophagous insects and cause severe diseases in humans. These infections pose a global threat, particularly in low-resource settings, and are increasingly extending beyond the current endemic regions. Tropism of parasites is crucial for their development, and recent studies have revealed colonization of noncanonical tissues, aiding their survival and immune evasion. Despite receiving limited attention, cumulative evidence discloses the respiratory system as a significant interface for host-pathogen interactions, influencing the course of (co)infection and disease onset. Due to its pathophysiological and clinical implications, we emphasize that further research is needed to better understand the involvement of the respiratory system and its potential to improve prevention, diagnosis, treatment, and interruption of the chain of transmission.
Assuntos
Plasmodium , Animais , Humanos , Plasmodium/fisiologia , Sistema Respiratório/parasitologia , Trypanosoma/fisiologia , Insetos/parasitologia , Insetos Vetores/parasitologia , Leishmania/fisiologia , Infecções por Protozoários/parasitologia , Infecções por Protozoários/transmissão , Leishmaniose/transmissão , Leishmaniose/parasitologiaRESUMO
Triatomines (kissing bugs) and tsetse flies (genus: Glossina) are natural vectors of Trypanosoma cruzi and Trypanosoma brucei, respectively. T. cruzi is the causative agent of Chagas disease, endemic in Latin America, while T. brucei causes African sleeping sickness disease in sub-Saharan Africa. Both triatomines and tsetse flies are host to a diverse community of gut microbiota that co-exist with the parasites in the gut. Evidence has shown that the gut microbiota of both vectors plays a key role in parasite development and transmission. However, knowledge on the mechanism involved in parasite-microbiota interaction remains limited and scanty. Here, we attempt to analyse Trypanosoma spp. and gut microbiota interactions in tsetse flies and triatomines, with a focus on understanding the possible mechanisms involved by reviewing published articles on the subject. We report that interactions between Trypanosoma spp. and gut microbiota can be both direct and indirect. In direct interactions, the gut microbiota directly affects the parasite via the formation of biofilms and the production of anti-parasitic molecules, while on the other hand, Trypanosoma spp. produces antimicrobial proteins to regulate gut microbiota of the vector. In indirect interactions, the parasite and gut bacteria affect each other through host vector-activated processes such as immunity and metabolism. Although we are beginning to understand how gut microbiota interacts with the Trypanosoma parasites, there is still a need for further studies on functional role of gut microbiota in parasite development to maximize the use of symbiotic bacteria in vector and parasite control.
Assuntos
Microbioma Gastrointestinal , Insetos Vetores , Moscas Tsé-Tsé , Animais , Moscas Tsé-Tsé/microbiologia , Moscas Tsé-Tsé/fisiologia , Moscas Tsé-Tsé/parasitologia , Microbioma Gastrointestinal/fisiologia , Insetos Vetores/microbiologia , Insetos Vetores/fisiologia , Trypanosoma cruzi/fisiologia , Triatominae/fisiologia , Triatominae/microbiologia , Triatominae/parasitologia , Trypanosoma brucei brucei/fisiologia , Trypanosoma/fisiologia , Interações Hospedeiro-ParasitaRESUMO
The squash bee Eucera (Peponapis) pruinosa is emerging as a model species to study how stressors impact solitary wild bees in North America. Here, we describe the prevalence of trypanosomes, microsporidians and mollicute bacteria in E. pruinosa and two other species, Bombus impatiens and Apis mellifera, that together comprise over 97% of the pollinator visitors of Cucurbita agroecosystems in Pennsylvania (United States). Our results indicate that all three parasite groups are commonly detected in these bee species, but E. pruinosa often exhibit higher prevalences. We further describe novel trypanosome parasites detected in E. pruinosa, however it is unknown how these parasites impact these bees. We suggest future work investigates parasite replication and infection outcomes.
Assuntos
Abelhas , Parasitos , Animais , Abelhas/microbiologia , Abelhas/parasitologia , Cucurbita , New England , Polinização , Prevalência , Estados Unidos , Trypanosoma/fisiologia , Microsporídios/fisiologia , Tenericutes/fisiologiaRESUMO
African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.
Assuntos
Glicoproteínas de Membrana/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma brucei brucei , Trypanosoma , Animais , Complemento C3 , Antígeno de Macrófago 1 , Mamíferos/metabolismo , Camundongos , Trypanosoma/fisiologia , Trypanosoma brucei brucei/metabolismoRESUMO
Trypanosoma theileri is considered a non- or low-pathogenic trypanosome that generally causes latent infection in apparently healthy cattle; however, T. theileri propagates in the bloodstream and may cause clinical disease in pregnant animals or co-infection with bovine leukemia virus or Theileria orientalis. In the current study, a monthly survey of T. theileri infection over one year was carried out in a research dairy farm in Hokkaido, Japan to determine the 1) seasonal variations in the prevalence, 2) genetic characterization of T. theileri, and 3) associations of milk and blood parameters in dairy cattle with T. theileri infection, including data of metabolic profile tests and dairy herd performance tests, using linear mixed models. We found that 1) the prevalence of T. theileri infection was significantly higher in summer and winter than in other seasons; 2) T. theileri possibly showed genetic diversity in Eastern Hokkaido; and 3) T. theileri infection was associated with significantly lower levels of blood urea nitrogen, milk protein, and solids-not-fat, which are caused by a low rumen fermentation level. This is the first study to report the negative impact of T. theileri infection in dairy cattle, and our study indicates that control of T. theileri infection can improve the productivity of dairy cattle.
Assuntos
Doenças dos Bovinos/epidemiologia , Indústria de Laticínios/economia , Variação Genética , Trypanosoma/fisiologia , Tripanossomíase/veterinária , Animais , Sangue/parasitologia , Bovinos , Doenças dos Bovinos/parasitologia , Japão/epidemiologia , Leite/parasitologia , Estações do Ano , Trypanosoma/genética , Tripanossomíase/epidemiologia , Tripanossomíase/parasitologiaRESUMO
In this study, single-SNP GWAS analyses were conducted to find regions affecting tolerance against trypanosomosis and morphometrics traits in purebred and crossbred Baoulé cattle of Burkina Faso. The trypanosomosis status (positive and negative) and a wide set of morphological traits were recorded for purebred Baoulé and crossbred Zebu x Baoulé cattle, and genotyped with the Illumina Bovine SNP50 BeadChip. After quality control, 36,203 SNPs and 619 animals including 343 purebred Baoulé and 279 crossbreds were used for the GWAS analyses. Several important genes were found that can influence morphological parameters. Although there were no genes identified with a reported strong connection to size traits, many of them were previously identified in various growth-related studies. A re-occurring theme for the genes residing in the regions identified by the most significant SNPs was pleiotropic effect on growth of the body and the cardiovascular system. Regarding trypanosomosis tolerance, two potentially important regions were identified in purebred Baoulé on chromosomes 16 and 24, containing the CFH, CRBN, TRNT1 and, IL5RA genes, and one additional genomic region in Baoulé, x Zebu crossbreds on chromosome 5, containing MGAT4C and NTS. Almost all of these regions and genes were previously related to the trait of interest, while the CRBN gene was to our knowledge presented in the context of trypanosomiasis tolerance for the first time.
Assuntos
Cruzamento , Bovinos/anatomia & histologia , Bovinos/parasitologia , Estudo de Associação Genômica Ampla , Trypanosoma/fisiologia , Animais , Burkina Faso , Bovinos/genética , Cromossomos de Mamíferos/genética , Polimorfismo de Nucleotídeo Único/genética , PrevalênciaRESUMO
As a relatively successful pathogen, several parasites can establish long-term infection in host. This "harmonious symbiosis" status relies on the "precise" manipulation of host immunity and metabolism, however, the underlying mechanism is still largely elusive. Immunometabolism is an emerging crossed subject in recent years. It mainly discusses the regulatory mechanism of metabolic changes on reprogramming the key transcriptional and post-transcriptional events related to immune cell activation and effect, which provides a novel insight for understanding how parasites regulate the infection and immunity in hosts. The present study reviewed the current research progress on metabolic reprogramming mechanism exploited by parasites to modulate the function in various immune cells, highlighting the future exploitation of key metabolites or metabolic events to clarify the underlying mechanism of anti-parasite immunity and design novel intervention strategies against parasitic infection.
Assuntos
Células Dendríticas/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Doenças Parasitárias/imunologia , Plasmodium/imunologia , Schistosoma/imunologia , Trypanosoma/imunologia , Animais , Células Dendríticas/metabolismo , Células Dendríticas/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Linfócitos/metabolismo , Linfócitos/parasitologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Doenças Parasitárias/metabolismo , Doenças Parasitárias/parasitologia , Plasmodium/fisiologia , Schistosoma/fisiologia , Trypanosoma/fisiologiaRESUMO
Meiosis is a core feature of eukaryotes that occurs in all major groups, including the early diverging excavates. In this group, meiosis and production of haploid gametes have been described in the pathogenic protist, Trypanosoma brucei, and mating occurs in the salivary glands of the insect vector, the tsetse fly. Here, we searched for intermediate meiotic stages among trypanosomes from tsetse salivary glands. Many different cell types were recovered, including trypanosomes in Meiosis I and gametes. Significantly, we found trypanosomes containing three nuclei with a 1:2:1 ratio of DNA contents. Some of these cells were undergoing cytokinesis, yielding a mononucleate gamete and a binucleate cell with a nuclear DNA content ratio of 1:2. This cell subsequently produced three more gametes in two further rounds of division. Expression of the cell fusion protein HAP2 (GCS1) was not confined to gametes, but also extended to meiotic intermediates. We propose a model whereby the two nuclei resulting from Meiosis I undergo asynchronous Meiosis II divisions with sequential production of haploid gametes.
Assuntos
Células Germinativas/metabolismo , Reprodução/fisiologia , Trypanosoma/genética , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , DNA/genética , Células Germinativas/fisiologia , Meiose/genética , Meiose/fisiologia , Trypanosoma/metabolismo , Trypanosoma/fisiologia , Moscas Tsé-Tsé/genéticaRESUMO
Much of the vast evolutionary landscape occupied by Eukaryotes is dominated by protists. Though parasitism has arisen in many lineages, there are three main groups of parasitic protists of relevance to human and livestock health: the Apicomplexa, including the malaria parasite Plasmodium and coccidian pathogens of livestock such as Eimeria; the excavate flagellates, encompassing a diverse range of protist pathogens including trypanosomes, Leishmania, Giardia and Trichomonas; and the Amoebozoa, including pathogenic amoebae such as Entamoeba. These three groups represent separate, deep branches of the eukaryote tree, underlining their divergent evolutionary histories. Here, I explore what is known about sex in these three main groups of parasitic protists.
Assuntos
Amebozoários/fisiologia , Apicomplexa/fisiologia , Reprodução/fisiologia , Trypanosoma/fisiologia , Animais , Apicomplexa/patogenicidade , DNA de Cinetoplasto , Eucariotos/fisiologia , Feminino , Células Germinativas/fisiologia , Estágios do Ciclo de Vida , Masculino , Infecções por Protozoários/parasitologia , Infecções por Protozoários/transmissãoRESUMO
Today, more than a billion people-one-sixth of the world's population-are suffering from neglected tropical diseases. Human African trypanosomiasis, Chagas disease, and leishmaniasis are neglected tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania About half a million people living in tropical and subtropical regions of the world are at risk of contracting one of these three infections. Kinetoplastids have complex life cycles with different morphologies and unique physiological requirements at each life cycle stage. This review covers the latest findings on metabolic pathways impacting disease pathogenesis of kinetoplastids within the mammalian host. Nutrient availability is a key factor shaping in vivo parasite metabolism; thus, kinetoplastids display significant metabolic flexibility. Proteomic and transcriptomic profiles show that intracellular trypanosomatids are able to switch to an energy-efficient metabolism within the mammalian host system. Host metabolic changes can also favor parasite persistence, and contribute to symptom development, in a location-specific fashion. Ultimately, targeted and untargeted metabolomics studies have been a valuable approach to elucidate the specific biochemical pathways affected by infection within the host, leading to translational drug development and diagnostic insights.
Assuntos
Adaptação Fisiológica , Metabolismo Energético , Infecções por Euglenozoa/metabolismo , Infecções por Euglenozoa/parasitologia , Interações Hospedeiro-Parasita , Leishmania/fisiologia , Trypanosoma/fisiologia , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Gerenciamento Clínico , Suscetibilidade a Doenças , Infecções por Euglenozoa/diagnóstico , Infecções por Euglenozoa/transmissão , Humanos , Redes e Vias MetabólicasRESUMO
Toxoplasma gondii can infect almost all warm-blooded vertebrates with pathogensis being largely influenced by the host immune status. As important epidemiological hosts, rodents are globally distributed and are also commonly found infected with haemoflagellates, such as those in the genus Trypanosoma. We here address whether and how co-infection with trypanosomes can influence T. gondii infection in laboratory models. Rats of five strains, co-infected with T. lewisi and mice of four strains, co-infected with T. musculi, were found to be more or less susceptible to T. gondii infection, respectively, with corresponding increased or decreased brain cyst burdens. Downregulation of iNOS expression and decreased NO production or reverse were observed in the peritoneal macrophages of rats or mice, infected with trypanosomes, respectively. Trypanosoma lewisi and T. musculi can modulate host immune responses, either by enhancement or suppression and influence the outcome of Toxoplasma infection.
Assuntos
Toxoplasmose/complicações , Trypanosoma lewisi/fisiologia , Tripanossomíase/complicações , Animais , Western Blotting , Encéfalo/parasitologia , Modelos Animais de Doenças , Macrófagos Peritoneais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Ratos Wistar , Organismos Livres de Patógenos Específicos , Esplenomegalia , Toxoplasma/fisiologia , Toxoplasmose/epidemiologia , Trypanosoma/classificação , Trypanosoma/fisiologia , Tripanossomíase/imunologia , Tripanossomíase/parasitologiaRESUMO
BACKGROUND: In the 1980s and 1990s, great strides were taken towards the elimination of tsetse and animal African trypanosomiasis (AAT) in Zimbabwe. However, advances in recent years have been limited. Previously freed areas have been at risk of reinvasion, and the disease in tsetse-infested areas remains a constraint to food security. As part of ongoing control activities, monitoring of tsetse and AAT is performed regularly in the main areas at risk. However, a centralized digital archive is missing. To fill this gap, a spatially explicit, national-level database of tsetse and AAT (i.e. atlas) was established through systematic data collation, harmonization and geo-referencing for the period 2000-2019. METHODS: The atlas covers an area of approximately 70,000 km2, located mostly in the at-risk areas in the north of the country. In the tsetse component, a total of 33,872 entomological records were assembled for 4894 distinct trap locations. For the AAT component, 82,051 samples (mainly dry blood smears from clinically suspicious animals) were collected at 280 diptanks and examined for trypanosomal infection by microscopy. RESULTS: Glossina pallidipes (82.7% of the total catches) and Glossina morsitans morsitans (17.3%) were the two tsetse species recorded in the north and northwest parts of the country. No fly was captured in the northeast. The distribution of AAT follows broadly that of tsetse, although sporadic AAT cases were also reported from the northeast, apparently because of transboundary animal movement. Three trypanosome species were reported, namely Trypanosoma brucei (61.7% of recorded infections), Trypanosoma congolense (28.1%) and Trypanosoma vivax (10.2%). The respective prevalences, as estimated in sentinel herds by random sampling, were 2.22, 0.43 and 0.30%, respectively. DISCUSSION: The patterns of tsetse and AAT distributions in Zimbabwe are shaped by a combination of bioclimatic factors, historical events such as the rinderpest epizootic at the turn of the twentieth century and extensive and sustained tsetse control that is aimed at progressively eliminating tsetse and trypanosomiasis from the entire country. The comprehensive dataset assembled in the atlas will improve the spatial targeting of surveillance and control activities. It will also represent a valuable tool for research, by enabling large-scale geo-spatial analyses.
Assuntos
Distribuição Animal , Trypanosoma/fisiologia , Tripanossomíase Africana/veterinária , Moscas Tsé-Tsé/parasitologia , Animais , Atlas como Assunto , Bases de Dados Factuais , Insetos Vetores/parasitologia , Gado/parasitologia , Trypanosoma/classificação , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/prevenção & controle , Zimbábue/epidemiologiaRESUMO
African trypanosomiasis (AT) is a neglected disease of both humans and animals caused by Trypanosoma parasites, which are transmitted by obligate hematophagous tsetse flies (Glossina spp.). Knowledge on tsetse fly vertebrate hosts and the influence of tsetse endosymbionts on trypanosome presence, especially in wildlife-human-livestock interfaces, is limited. We identified tsetse species, their blood-meal sources, and correlations between endosymbionts and trypanosome presence in tsetse flies from the trypanosome-endemic Maasai Mara National Reserve (MMNR) in Kenya. Among 1167 tsetse flies (1136 Glossina pallidipes, 31 Glossina swynnertoni) collected from 10 sampling sites, 28 (2.4%) were positive by PCR for trypanosome DNA, most (17/28) being of Trypanosoma vivax species. Blood-meal analyses based on high-resolution melting analysis of vertebrate cytochrome c oxidase 1 and cytochrome b gene PCR products (n = 354) identified humans as the most common vertebrate host (37%), followed by hippopotamus (29.1%), African buffalo (26.3%), elephant (3.39%), and giraffe (0.84%). Flies positive for trypanosome DNA had fed on hippopotamus and buffalo. Tsetse flies were more likely to be positive for trypanosomes if they had the Sodalis glossinidius endosymbiont (P = 0.0002). These findings point to complex interactions of tsetse flies with trypanosomes, endosymbionts, and diverse vertebrate hosts in wildlife ecosystems such as in the MMNR, which should be considered in control programs. These interactions may contribute to the maintenance of tsetse populations and/or persistent circulation of African trypanosomes. Although the African buffalo is a key reservoir of AT, the higher proportion of hippopotamus blood-meals in flies with trypanosome DNA indicates that other wildlife species may be important in AT transmission. No trypanosomes associated with human disease were identified, but the high proportion of human blood-meals identified are indicative of human African trypanosomiasis risk. Our results add to existing data suggesting that Sodalis endosymbionts are associated with increased trypanosome presence in tsetse flies.
Assuntos
Animais Selvagens/parasitologia , Insetos Vetores/parasitologia , Gado/parasitologia , Simbiose/fisiologia , Trypanosoma/fisiologia , Moscas Tsé-Tsé/parasitologia , Animais , Artiodáctilos/parasitologia , Sangue , Búfalos/parasitologia , Ecossistema , Elefantes/parasitologia , Enterobacteriaceae , Humanos , Quênia , Reação em Cadeia da Polimerase , Trypanosoma/genética , Trypanosoma vivax , Tripanossomíase Africana/parasitologiaRESUMO
The family Hippoboscidae is a less known group of blood-sucking flies. Deer ked are particularly important for animal health; they may act as potential vectors of disease to ungulates, and may transmit pathogens to animals and humans. The aim of this study was to investigate the presence of Trypanosoma (Megatrypanum) DNA in deer keds using molecular methods. Results prove the presence of Megatrypanum trypanosome DNA in the studied winged adult deer keds and this is the first detection of this pathogen in Lipoptena fortisetosa. In addition, this paper evidences the occurrence of L. fortisetosa in two new locations: one in the Bialowieza Primeval Forest, and another in the Strzalowo Forest Inspectorate (Piska Forest), both in north-eastern Poland.
Assuntos
Dípteros/parasitologia , Interações Hospedeiro-Parasita , Trypanosoma/isolamento & purificação , Distribuição Animal , Animais , DNA de Protozoário/análise , Dípteros/fisiologia , Polônia , Trypanosoma/fisiologiaRESUMO
African animal trypanosomiasis (AAT), a disease complex caused by tsetse fly-transmitted Trypanosoma brucei brucei, T. congolense savannah ITS, and T. vivax, continues to inflict heavy losses to the animal industry in terms of decreased livestock production and productivity. Live bait technology and chemotherapy have been used as a control strategy in northern Uganda since 2006 with minimal success. Here, we report the results of a cross-sectional study carried out in Lango subregion, Uganda, to assess the species prevalence of bovine trypanosome in cattle using the internal transcribed spacer (ITS) of trypanosome ribosomal DNA (rDNA). Blood samples were collected from 1090 cattle by ear vein puncture and screened using a single pair of primers designed to amplify ITS ribosomal DNA (rDNA). Our results indicate an overall prevalence of 40.18% (438/1090, 95% CI 30.82-54.51). T. vivax constituted 32.66% (356/1090), T. congolense 2.39% (26/1090), T. brucei 1.28% (14/1090), T. godfreyi 0.09%(1/1090), T. brucei and T. congolense 0.36% (4/1090), T. brucei and T. vivax 1.47% (16/1090), T. vivax and T. congolense 1.65% (18/1090), T. vivax and T. simiae 0.18% (2/1090), and T. vivax and T. godfreyi 0.09% (1/1090) of infections. Over 91.7% of infections involved single species, while 9.5% were mixed infections. Over 90.2% (37/41) of the mixed infections involved T. vivax as one of the species, while 53.7% (22/41) involved T. congolense. The high prevalence of AAT and the continued presence of T. brucei raise public health concerns because of the zoonotic implications. An integrated approach that involves mass treatment of cattle, vector, and animal movement control should be adopted to reduce the risk of both AAT and HAT.
Assuntos
Tripanossomíase Bovina/epidemiologia , Tripanossomíase Bovina/prevenção & controle , Animais , Bovinos , Estudos Transversais , DNA de Protozoário/análise , DNA Espaçador Ribossômico/análise , Prevalência , Trypanosoma/fisiologia , Uganda/epidemiologiaRESUMO
BACKGROUND: The subgenus Megatrypanum Hoare, 1964 of Trypanosoma Gruby, 1843 comprises trypanosomes of cervids and bovids from around the world. Here, the white-tailed deer Odocoileus virginianus (Zimmermann) and its ectoparasite, the deer ked Lipoptena mazamae Rondani, 1878 (hippoboscid fly), were surveyed for trypanosomes in Venezuela. RESULTS: Haemoculturing unveiled 20% infected WTD, while 47% (7/15) of blood samples and 38% (11/29) of ked guts tested positive for the Megatrypanum-specific TthCATL-PCR. CATL and SSU rRNA sequences uncovered a single species of trypanosome. Phylogeny based on SSU rRNA and gGAPDH sequences tightly cluster WTD trypanosomes from Venezuela and the USA, which were strongly supported as geographical variants of the herein described Trypanosoma (Megatrypanum) trinaperronei n. sp. In our analyses, the new species was closest to Trypanosoma sp. D30 from fallow deer (Germany), both nested into TthII alongside other trypanosomes from cervids (North American elk and European fallow, red and sika deer), and bovids (cattle, antelopes and sheep). Insights into the life-cycle of T. trinaperronei n. sp. were obtained from early haemocultures of deer blood and co-culture with mammalian and insect cells showing flagellates resembling Megatrypanum trypanosomes previously reported in deer blood, and deer ked guts. For the first time, a trypanosome from a cervid was cultured and phylogenetically and morphologically (light and electron microscopy) characterised. CONCLUSIONS: In the analyses based on SSU rRNA, gGAPDH, CATL and ITS rDNA sequences, neither cervids nor bovids trypanosomes were monophyletic but intertwined within TthI and TthII major phylogenetic lineages. One host species can harbour more than one species/genotype of trypanosome, but each trypanosome species/genotype was found in a single host species or in phylogenetically closely related hosts. Molecular evidence that L. mazamae may transmit T. trinaperronei n. sp. suggests important evolutionary constraints making tight the tripartite T. trinaperronei-WTD-deer ked association. In a plausible evolutionary scenario, T. trinaperronei n. sp. entered South America with North American white-tailed deer at the Pliocene-Pleistocene boundary following the closure of the Panama Isthmus.
Assuntos
Doença de Chagas/veterinária , Cervos/parasitologia , Dípteros/parasitologia , Ectoparasitoses/veterinária , Trypanosoma/classificação , Trypanosoma/fisiologia , Animais , Evolução Biológica , DNA Ribossômico/genética , Feminino , Genótipo , Especificidade de Hospedeiro , Masculino , Microscopia Eletrônica , Filogenia , Filogeografia , RNA Ribossômico 18S/genética , Trypanosoma/ultraestrutura , VenezuelaRESUMO
In this study, the expression of pro-inflammatory and iron metabolism genes were analysed under Trypanoplasma borreli (T. borreli) challenge in common carp. Three transferrin (Tf) genotypic groups: two homozygous - DD, GG, and heterozygous DG were intraperitoneally infected with a dose of 2.16 × 105/100 µL parasites. Organ and blood samples were collected at weekly intervals. During the infection period, mortality and parasitaemia were assessed along with measurements of blood iron concentrations and antibody levels. Expression of Tf, Fer, IRP1 and 2, TfR 1a and 1b, Hep, TNF α1 and α2, and IL-1 ß was measured in the peak of parasitaemia and the week preceding the peak. Study revealed, that changes in iron blood level induced by parasite were not correlated with the activities of iron homeostasis genes. Neither iron content nor the specific antibody response correlated with survival. We demonstrate that challenged carp, display three distinct, Tf genotype dependent activity patterns of iron homeostasis genes expression. The expected, "classical" way of up-regulation represented homozygous DD individuals. In contrast, GG individuals demonstrated downward trend, while gene expressions of heterozygous DG carp could be defined as an intermediate. We speculate, whether this phenomenon is related to the transferrin molecule itself or to Tf-genotypes being markers of other factors, that influence the iron homeostasis genes activities. We discussed the role of alarmins in triggering the immune response. Distinct genes activating patterns of homozygous genotypes DD and GG had no consequences in terms of mortality rates caused by T.borreli. The highest mortality was observed in the heterozygous group DG. In conclusion, this study suggest that transferrin variant, but not iron blood concentration, has a significant impact on carp immune response to blood parasite infection. This research sheds a new light on the inflammation process and interaction between a host and invaders.
Assuntos
Carpas/imunologia , Doenças dos Peixes/imunologia , Imunidade/genética , Transferrina/imunologia , Animais , Carpas/genética , Feminino , Genótipo , Masculino , Transferrina/genética , Trypanosoma/fisiologia , Tripanossomíase/imunologia , Tripanossomíase/veterináriaRESUMO
Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.
Assuntos
Fator H do Complemento/metabolismo , Trypanosoma/fisiologia , Moscas Tsé-Tsé/parasitologia , Animais , Anticorpos Monoclonais/metabolismo , Células CHO , Bovinos , Membrana Celular/metabolismo , Complemento C3b/metabolismo , Fator H do Complemento/química , Cricetinae , Cricetulus , Camundongos Endogâmicos BALB C , Parasitemia/sangue , Ligação Proteica , Domínios Proteicos , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Receptores de Superfície Celular/metabolismo , Regulação para CimaRESUMO
The recent endorsement of fexinidazole by the European Medicines Agency for the treatment of human African trypanosomiasis has demonstrated the high predictive value of cell-based assays for parasite chemotherapy. Here we describe three in vitro drug susceptibility tests with Trypanosoma brucei that have served as the basis for the identification of fexinidazole as a promising lead: (1) a standard assay with end-point measurement to determine drug efficacy; (2) a wash-out assay to test for reversibility and speed of drug action; (3) isothermal microcalorimetry for real-time measurement of onset of drug action and time to kill. Together, these assays allow to estimate pharmacodynamic parameters in vitro and to devise appropriate treatment regimens for subsequent in vivo experiments.
Assuntos
Testes de Sensibilidade Parasitária/métodos , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Tripanossomíase Africana/tratamento farmacológico , Calorimetria/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma/fisiologia , Tripanossomíase Africana/sangue , Tripanossomíase Africana/parasitologiaRESUMO
During a blood meal, female Anopheles mosquitoes are potentially exposed to diverse microbes in addition to the malaria parasite, Plasmodium. Human and animal African trypanosomiases are frequently co-endemic with malaria in Africa. It is not known whether exposure of Anopheles to trypanosomes influences their fitness or ability to transmit Plasmodium. Using cell and molecular biology approaches, we found that Trypanosoma brucei brucei parasites survive for at least 48h after infectious blood meal in the midgut of the major malaria vector, Anopheles coluzzii before being cleared. This transient survival of trypanosomes in the midgut is correlated with a dysbiosis, an alteration in the abundance of the enteric bacterial flora in Anopheles coluzzii. Using a developmental biology approach, we found that the presence of live trypanosomes in mosquito midguts also reduces their reproductive fitness, as it impairs the viability of laid eggs by affecting their hatching. Furthermore, we found that Anopheles exposure to trypanosomes enhances their vector competence for Plasmodium, as it increases their infection prevalence. A transcriptomic analysis revealed that expression of only two Anopheles immune genes are modulated during trypanosome exposure and that the increased susceptibility to Plasmodium was microbiome-dependent, while the reproductive fitness cost was dependent only on the presence of live trypanosomes but was microbiome independent. Taken together, these results demonstrate multiple effects upon Anopheles vector competence for Plasmodium caused by eukaryotic microbes interacting with the host and its microbiome, which may in turn have implications for malaria control strategies in co-endemic areas.