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Sent on Wednesday, 2009 May 27Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
- 1: PLoS Negl Trop Dis. 2009 May 26;3(5):e441.
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Leishmania infantum Amastigotes Enhance HIV-1 Production in Cocultures of Human Dendritic Cells and CD4 T Cells by Inducing Secretion of IL-6 and TNF-alpha.
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Faculté de Médecine, Université Laval, Québec, Québec, Canada.
BACKGROUND: Visceral leishmaniasis has emerged as an important opportunistic disease among patients infected with HIV-1. Both HIV-1 and the protozoan parasite Leishmania can productively infect cells of the macrophage-dendritic cell lineage. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that Leishmania infantum amastigotes increase HIV-1 production when human primary dendritic cells (DCs) are cocultured together with autologous CD4(+) T cells. Interestingly, the promastigote form of the parasite does not modulate virus replication. Moreover, we report that amastigotes promote virus replication in both cell types. Our results indicate that this process is due to secretion of parasite-induced soluble factors by DCs. Luminex micro-beads array system analyses indicate that Leishmania infantum amastigotes induce a higher secretion of several cytokines (i.e. IL-1alpha, IL-2, IL-6, IL-10 and TNF-alpha) and chemokines (i.e. MIP-1alpha, MIP-1beta and RANTES) in these cells. Studies conducted with pentoxifylline and neutralizing antibodies revealed that the Leishmania-dependent augmentation in HIV-1 replication is due to a higher secretion of IL-6 and TNF-alpha. CONCLUSIONS/SIGNIFICANCE: Altogether these findings suggest that the presence of Leishmania within DC/T-cell conjugates leads to an enhancement of virus production and demonstrate that HIV-1 and Leishmania can establish complex interactions in such a cellular microenvironment.
PMID: 19468304 [PubMed - in process]
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- ReviewCytokines and HIV-1: interactions and clinical implications.
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- Leishmania infantum promotes replication of HIV type 1 in human lymphoid tissue cultured ex vivo by inducing secretion of the proinflammatory cytokines TNF-alpha and IL-1 alpha.
- 2: Glycobiology. 2009 May 25. [Epub ahead of print]
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Molecular analysis of a UDP-GlcNAc:polypeptide {alpha}-N-acetylglucosaminyltransferase implicated in the initiation of mucin-type O-glycosylation in Trypanosoma cruzi.
Dept. of Biochemistry & Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Trypanosoma cruzi, the causative agent of Chagas disease, is surrounded by a mucin coat that plays important functions in parasite survival/invasion and is extensively O-glycosylated by Golgi and cell surface glycosyltransferases. Addition of the first sugar, alpha-N-acetylglucosamine (GlcNAc) linked to Threonine (Thr), is catalyzed by a polypeptide alpha-GlcNAc-transferase (pp-alphaGlcNAcT) which is unstable to purification. Here, a comparison of the genomes of T. cruzi and Dictyostelium discoideum, an amoebazoan which also forms this linkage, identified two T. cruzi genes (TcOGNT1 and TcOGNT2) that might encode this activity. Though neither was able to complement the Dictyostelium gene, expression in the trypanosomatid Leishmania tarentolae resulted in elevated levels of UDP-[(3)H]GlcNAc:Thr-peptide GlcNAc-transferase activity and UDP-[(3)H]GlcNAc breakdown activity. The ectodomain of TcOGNT2 was expressed and the secreted protein found to retain both activities after extensive purification away from other proteins and the endogenous activity. Product analysis showed that (3)H was transferred as GlcNAc to a hydroxyamino acid, and breakdown was due to hydrolysis. Both activities were specific for UDP-GlcNAc relative to UDP-GalNAc, and were abolished by active site point mutations that inactivate a related Dictyostelium enzyme and distantly related animal pp-alphaGalNAcTs. The peptide preference and the alkaline pH optimum were indistinguishable from that of the native activity in T. cruzi microsomes. The results suggest that mucin-type O-glycosylation in T. cruzi is initiated by conserved members of CAZy family GT60, which is homologous to the GT27 family of animal pp-alphaGalNAcTs that initiate mucin-type O-glycosylation in animals.
PMID: 19468051 [PubMed - as supplied by publisher]
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- Biosynthesis of O-N-acetylglucosamine-linked glycans in Trypanosoma cruzi. Characterization of the novel uridine diphospho-N-acetylglucosamine:polypeptide N-acetylglucosaminyltransferase-catalyzing formation of N-acetylglucosamine alpha1-->O-threonine.
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- Initiation of mucin-type O-glycosylation in dictyostelium is homologous to the corresponding step in animals and is important for spore coat function.
- 3: Acta Trop. 2009 Mar 5. [Epub ahead of print]
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What is the role of small rodents in the transmission cycle of Trypanosoma cruzi and Trypanosoma evansi (Kinetoplastida Trypanosomatidae)? A study case in the Brazilian Pantanal.
Center for Infectious Disease Dynamics, The Pennsylvania State University, Biology Department, 208 Mueller Lab, University Park, PA, 16802-5301, USA; Laboratório de Biologia e Parasitologia de Mamíferos Silvestres Reservatórios, Departamento de Medicina Tropical, FIOCRUZ/RJ, Av Brasil 4365, Rio de Janeiro, RJ, 21045-900, Brazil.
Determining the reservoir hosts for parasites is crucial for designing control measures, but it is often difficult to identify the role that each host species plays in maintaining the cycle of infection in the wild. One way to identify potential maintenance hosts is to estimate key parameters associated with transmission and pathogenicity. Here we assess the potential for three native rodent species of the Brazilian Pantanal (Clyomys laticeps, Thrichomys pachyurus and Oecomys mamorae) to act as reservoir or maintenance hosts of Trypanosoma evansi, an important parasite of domestic livestock. By analyzing blood parameters of naturally infected wild-caught rodents of these species, we compared their levels of parasitemia and anemia due to T. evansi infection with literature values for other host species infected by this parasite. We also analyzed levels of these blood parameters relative to infection by Trypanosoma cruzi, the causative agent of Chagas disease in humans, for which wild rodents are already thought to be important reservoir species. All three species showed low impacts of the two trypanosomes on their blood parameters compared to other species, suggesting that they experience a low virulence of trypanosome infection under natural conditions in the Pantanal and might act as maintenance hosts of trypanosome infections. The low parasitemia of trypanosome infections suggests that these rodents play a secondary role in the transmission cycle compared to other species, especially compared to the capybara (Hydrochaeris hydrochaeris) which also experiences low pathogenicity due to infection despite much higher levels of parasitemia.
PMID: 19467452 [PubMed - as supplied by publisher]
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Parasitol Res. 2008 Aug; 103(3):619-24. Epub 2008 May 22.
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- 4: J Am Acad Dermatol. 2009 Jun;60(6):897-925.
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Tropical dermatology: Tropical diseases caused by protozoa.
Department of Dermatology at Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both Africa and South America. Amebiasis, a less common protozoal infection, is a cause of significant morbidity in some regions. Toxoplasmosis and pneumocystosis (formerly thought to be caused by a protozoan) are worldwide parasitic infections with a very high incidence in immunocompromised patients but are not restricted to them. In the past, most protozoan infections were restricted to specific geographic areas and natural reservoirs. There are cases in which people from other regions may have come in contact with these pathogens. A common situation involves an accidental contamination of a traveler, tourist, soldier, or worker that has contact with a reservoir that contains the infection. Protozoan infections can be transmitted by arthropods, such as sandflies in the case of leishmaniasis or bugs in the case of trypanosomiases. Vertebrates also serve as vectors as in the case of toxoplasmosis and its transmission by domestic cats. The recognition of the clinical symptoms and the dermatologic findings of these diseases, and a knowledge of the geographic distribution of the pathogen, can be critical in making the diagnosis of a protozoan infection. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to recognize the significance of protozoan infections worldwide, identify the dermatologic manifestations of protozoan infections, and select the best treatment for the patient with a protozoan infection.
PMID: 19467364 [PubMed - in process]
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- 5: Acta Trop. 2009 May 22. [Epub ahead of print]
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Cutaneous leishmaniasis caused by Leishmania (L.) major infection in Sindh province, Pakistan.
Department of Dermatology, Chandka Medical College, Larkana, Pakistan.
Leishmaniasis is endemic in Pakistan and is wide-spread throughout the country. Polymerase chain reaction (PCR) was performed to identify the Leishmania species present in cutaneous leishmaniasis (CL) patients from new endemic areas of the central part of Sindh province, Pakistan. The PCR primers used were designed for the identification and differentiation of L. (L.) major and L. (L.) tropica species, and PCR bands at 620 and 830bp of the parasite-specific kinetoplast DNA sequences was identified for L. (L.) major and L. (L.) tropica, respectively. Among a total of 144 DNA samples purified from the skin biopsies of clinically suspected CL patients, 108 (75%) were positive for PCR amplification. Out of the 108 cases, 105 (97.2%) were determined to be positive for L. (L.) major infection, and 3 (2.8%) were positive for L. (L.) tropica infection. It was concluded that CL caused by L. (L.) major is the main source of infection in the central part of Sindh province in Pakistan. This rapid screening technique could be used for the diagnosis of a large number of samples from skin lesions, which commonly contain other bacterial and fungal infections.
PMID: 19467219 [PubMed - as supplied by publisher]
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- 6: Acta Trop. 2009 May 22. [Epub ahead of print]
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Molecular diagnosis of canine visceral leishmaniasis: Identification of Leishmania species by PCR-RFLP and quantification of parasite DNA by real-time PCR.
Laboratório de Leishmanioses, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Avenida Augusto de Lima, 1715 Barro Preto, 30190-002 Belo Horizonte, Minas Gerais, Brazil.
The efficacies of polymerase chain reaction (PCR) procedures for the diagnosis of canine visceral leishmaniasis (CVL), and of PCR-restriction fragment length polymorphism (RFLP) analysis for the identification of Leishmania species, have been assessed. Quantitative real-time PCR employing a SYBR Green dye-based system was standardised for the quantification of Leishmania kDNA minicircles. Skin, peripheral blood and bone marrow samples collected from 217 dogs, asymptomatic or symptomatic for CVL, were analysed. The PCR method, which was based on the amplification of a 120bp kDNA fragment conserved across Leishmania species, was able to detect the presence in clinical samples of protozoan parasite DNA in amounts as low as 0.1 fg. Bone marrow and skin samples proved to be more suitable than peripheral blood for the detection of Leishmania by PCR and presented positive indices of 84.9 and 80.2%, respectively. PCR-RFLP analysis indicated that 192 of the PCR-positive dogs were infected with Leishmaniainfantum chagasi, whilst L. braziliensis was identified in two other animals. Quantitative PCR revealed that bone marrow samples from dogs presenting positive conventional tests contained a higher number of copies of Leishmania kDNA than peripheral blood, although no significant differences were detected between symptomatic and asymptomatic dogs in terms of parasite load. This study demonstrates that PCR can be used for the detection of Leishmania in clinical samples derived from naturally infected dogs, and that PCR-RFLP represents a rapid and sensitive tool for the identification of Leishmania species. Additionally, qPCR is effective in quantifying Leishmania DNA load in clinical samples.
PMID: 19467216 [PubMed - as supplied by publisher]
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Vet Parasitol. 2007 Mar 31; 144(3-4):234-41. Epub 2006 Dec 28.
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T-bet inhibits the in vivo differentiation of parasite-specific CD4+ Th17 cells in a T cell-intrinsic manner.
Department of Microbiology and Immunology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298, USA.
CD4(+) Th17 cells have emerged as a new T cell subset in the Th1/Th2 paradigm, and efforts have shifted toward understanding the factors that regulate their development in vivo. To analyze the role of the transcription factor T-bet in regulation of Th17 cells, we used a murine model of Trypanosoma cruzi infection, a protozoan parasite that causes Chagas disease in humans. Infection of Tbx21(-/-) mice led to normal, unimpaired development of Ag-specific CD4(+) T cells producing IFN-gamma. However, a robust Th17 response developed concomitant with Th1 responses. Despite significant IFN-gamma production, the physiological effects of Th17 responses prevailed as there was a sharp increase in Gr-1(+)Ly6G(+) neutrophils. Adoptive transfer of T cells from infected Tbx21(-/-) mice into Rag-2(-/-) mice (Tbx21(+/+)) revealed that CD4(+) T cells maintained their IL-17-producing phenotype, including those cells capable of producing both IFN-gamma and IL-17. Furthermore, and in contrast to the effects of IL-2 on Th17 development, IL-2 had no effect on IL-17 production by primed T cells. Importantly, adoptive transfer of T cells from naive Tbx21(-/-) mice into infected Rag-2(-/-) mice recapitulated the differentiation of T. cruzi-specific Th17 cells observed in infected Tbx21(-/-) mice. Conversely, transfer of wild-type T cells into infected Tbx21(-/-) mice did not reveal an increase in Th17 development. These results demonstrate that T-bet regulates the differentiation of T. cruzi-specific Th17 cells in vivo in a T cell-intrinsic manner. These data provide important insight into the role of T-bet in regulation of parasite-specific Th17 responses.
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Diagnostic value of rectal temperature of African cattle of variable coat colour infected with trypanosomes and tick-borne infections.
National Livestock Resources Research Institute, Tororo, Uganda. Magonaw@live.com
Diagnosis of major endemic bovine parasitic diseases in sub-Saharan Africa such as trypanosomosis, theileriosis, anaplasmosis, babesiosis and cowdriosis is increasingly relying on clinical diagnosis due to deterioration of veterinary services and laboratory facilities. Pyrexia is a common clinical feature of aforementioned diseases whose detection relies on measurement of rectal temperature. The research undertaken in this study was aimed at assessing the effects of diurnal changes and variable coat colour of indigenous Nkedi Zebu cattle on the diagnostic value of rectal temperature under tropical conditions. The results revealed that variation in rectal temperature was significantly influenced by time of day it was taken and by the coat colour of the Nkedi Zebu cattle (P<0.001). Rectal temperature experienced diurnal changes: steadily rising to reach a peak at 17.00h before declining. The mean rectal temperature of unhealthy cattle was significantly higher (P<0.05) than that of the healthy ones only between 13.00 and 17.00h of the day. During which period the proportion of unhealthy cattle having a rectal temperature of 39.4 degrees C or higher was significantly higher than that of healthy ones (P<0.001). Regarding the variable coat colour of indigenous breeds, rectal temperature among cattle of different coat colours was significantly different (P<0.05). In conclusion it is important to consider diurnal changes in rectal temperature and differences due to variable coat colour of indigenous African breeds when measuring rectal temperature for assessing pyrexia, during clinical diagnosis of bovine trypanosomosis and tick-borne diseases that are endemic in many countries in sub-Saharan Africa.
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