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Sent on Wednesday, 2010 Oct 13Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Immunol. 2010 Oct 11. [Epub ahead of print]The Regulation of Th1 Responses by the p38 MAPK.Yang Z, Zhang X, Darrah PA, Mosser DM.Department of Cell Biology and Molecular Genetics and. AbstractIL-12 is a dimeric cytokine that is produced primarily by APCs. In this study we examined the role that the p38 MAPKs (MAPK/p38) play in regulating IL-12 production. We show that inhibition of p38 dramatically increased IL-12 production upon stimulation, while decreasing TNF-α. This reciprocal effect on these two cytokines following MAPK/p38 inhibition occurred in many different APCs, following a variety of different stimuli. IL-12 production was also increased in macrophages treated with small interfering RNA to limit p38α expression, and in macrophages deficient in MKK3, a kinase upstream of p38. The increase in IL-12 production following MAPK/p38 inhibition appears to be due to enhanced IL-12 (p40) mRNA stability. We show that MAPK/p38 inhibition can promote Th1 immune responses and thereby enhance vaccine efficacy against leishmaniasis. In a mouse model of Leishmania major infection, vaccination with heat-killed L. major plus CpG and SB203580 elicited complete protection against infection compared with heat-killed L. major plus CpG without SB203580. Thus, this work suggests that MAPK/p38 inhibitors may be applied as adjuvants to bias immune responses and improve vaccinations against intracellular pathogens. |
| PMID: 20937847 [PubMed - as supplied by publisher] | |
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| 2. | Infect Immun. 2010 Oct 11. [Epub ahead of print]Leukocytes infiltrating the skin and draining lymph nodes in response to the protozoan Leishmania infantum chagasi.< a href="http://www.ncbi.nlm.nih.gov/pubmed?term=%22Thalhofer%20CJ%22%5BAuthor%5D">Thalhofer CJ, Chen Y, Sudan B, Love-Homan L, Wilson ME.Interdisciplinary Immunology Program and the Departments of Internal Medicine, Microbiology and Epidemiology University of Iowa, and the Veterans' Affairs Medical Center, Iowa City, IA 52242. AbstractThe vector-borne protozoan Leishmania infantum chagasi (Lic) causes minimal inflammation after inoculation into skin, but disseminates to cause fatal visceral leishmaniasis. To define the inflammatory response at the parasite inoculation site, we introduced metacyclic Lic promastigotes intradermally into BALB/c mouse ears and studied inflammatory cells over 7 days. Ly6G(+) neutrophils rapidly infiltrated the dermis, peaking after 6-24 hrs. Macrophages and NK cells next infiltrated the dermis, and NK followed by B cells expanded in draining lymph nodes. Parasite-containing phagocytes were tracked with fluorescent mCherry(+)-Lic. Ly6G(+) neutrophils contained most intracellular parasites 6 to 24 hrs after inoculation, whereas dermal macrophages harbored most parasites after 2 to 7 days. These observations were validated microscopically. Low dose antibody transiently depleted mice of neutrophils, leaving other cells intact. Combined results of in vivo imaging, flow cytometry and quantitative PCR showed that neutrophil depletion slowed the clearance of extracellular (luciferase(+)) promastigotes during the first 24 hr after inoculation, yet decreased the numbers of leukocytes containing intracellular (mCherry+) parasites. From 3 days onward, total Lic-containing dermal leukocytes and total Lic in draining lymph nodes were similar in both groups. Nonetheless, a second wave of Lic-containing neutrophils occurred 7 days after parasite inoculation into neutrophil-depleted mice, corresponding to the time of neutrophil recovery. Thus, neutrophils were recruited to the dermis even late after inoculation, and Lic trafficked through neutrophils in both neutrophil-depleted and control mice, albeit with different kinetics. Recruitment of neutrophils, and transient parasite residence in neutrophils, may play a role in non-ulcerative forms of leishmaniasis. |
| PMID: 20937764 [PubMed - as supplied by publisher] | |
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| 3. | Top Companion Anim Med. 2010 Aug;25(3):149-54.Update on the Diagnosis and Management of Leishmania spp Infections in Dogs in the United States.Freeman K. |
| PMID: 20937498 [PubMed - in process] | |
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| 4. | Parasit Vectors. 2010 Oct 12;3(1):94. [Epub ahead of print]Study of house-level risk factors associated in the transmission of Indian Kala-azar.Kesari S, Bhunia GS, Kumar V, Jeyaram A, Ranjan A, Das P.AbstractABSTRACT: BACKGROUND: In visceral leishmaniasis (VL), phlebotomine vectors are the main target to reduce for control measures. An attempt has been taken to delineate the association between Phlebotomous argentipes and housing characteristics between two districts e.g. endemic and non-endemic. METHODS: A cross-sectional survey was conducted on 240 households for both the endemic (Vaishali district) and non-endemic (Lohardaga district) site. Logistic regression analysis was used to identify factors related to housing characteristics influencing suitable habitats for P. argentipes. Vector density estimated using a CDC light trap. RESULTS: The proportion of P. argentipes in both endemic and non-endemic areas was significantly much higher (P<0.001) when compared with the proportion of Sergentomiya and P. papatasi. The results of multilevel logistic regression analysis showed that mud plastered wall (P value = 0.001), mixed dwelling (P value = 0.002) and area (P value=0.001) were strongly associated with the presence of vectors. CONCLUSION: Result of the studied household characteristics provides an accurate, rapid assessment of house-level variation in risk. The results also have implications for maximizing surveillance efficacy of sandflies, which is likely to become increasingly important while formulating any control strategy. |
| PMID: 20937154 [PubMed - as supplied by publisher] | |
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| 5. | RNA. 2010 Oct;16(10):1951-67. Epub 2010 Aug 16.OB-fold domain of KREPA4 mediates high-affinity interaction with guide RNA and possesses annealing activity.Kala S, Salavati R.Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada. AbstractKREPA4, also called MP24, is an essential mitochondrial guide RNA (gRNA)-binding protein with a preference for the 3' oligo(U) tail in trypanosomes. Structural prediction and compositional analysis of KREPA4 have identified a conserved OB (oligonucleotide/oligosaccharide-binding)-fold at the C-terminal end and two low compositional complexity regions (LCRs) at its N terminus. Concurrent with these predictions, one or both of these regions in KREPA4 protein may be involved in gRNA binding. To test this possibility, deletion mutants of KREPA4 were made and the effects on the gRNA-binding affinities were measured by quantitative electrophoretic mobility shift assays. The gRNA-binding specificities of these mutants were evaluated by competition experiments using gRNAs with U-tail deletions or stem-loop modifications and uridylated nonguide RNAs or heterologous RNA. Our results identified the predicted OB-fold as the functional domain of KREPA4 that mediates a high-affinity interaction with the gRNA oligo(U) tail. An additional contribution toward RNA-binding function was localized to LCRs that further stabilize the binding through sequence-specific interactions with the guide secondary structure. In this study we also found that the predicted OB-fold has an RNA annealing activity, representing the first report of such activity for a core component of the RNA editing complex. |
| PMID: 20713467 [PubMed - indexed for MEDLINE] | |
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| 6. | Trends Parasitol. 2010 Jul;26(7):324-8. Epub 2010 Apr 8.African trypanosomes: celebrating diversity.Adams ER, Hamilton PB, Gibson WC.Koninklijk Instituut voor de Tropen (KIT) Biomedical Research, Amsterdam 1105 AZ, Netherlands. AbstractRecent advances in molecular identification techniques and phylogenetic analysis have revealed the presence of previously unidentified tsetse-transmitted trypanosomes in Africa. This is surprising in a comparatively well-known group of pathogens that includes the causative agents of human and animal trypanosomiasis. Despite levels of genetic divergence that warrant taxonomic recognition, only one of these new trypanosomes has been named as a new species; the increased diversity is largely ignored or regarded as an inconvenient complication. Yet, some of these trypanosomes have demonstrated pathogenicity, whereas others are closely related to known pathogens, and might share this trait. We should first acknowledge that these novel trypanosomes exist and then take steps to investigate their host range, pathogenicity to livestock and response to chemotherapy. |
| PMID: 20382076 [PubMed - indexed for MEDLINE] | |
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| 7. | Glycobiology. 2010 Jul;20(7):833-42. Epub 2010 Mar 30.Identification of glycoproteins targeted by Trypanosoma cruzi trans-sialidase, a virulence factor that disturbs lymphocyte glycosylation.Muiá RP, Yu H, Prescher JA, Hellman U, Chen X, Bertozzi CR, Campetella O.Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, B1650WGA San Martín, Argentina. AbstractTrypanosoma cruzi, the agent of the American trypanosomiasis or Chagas disease, bypasses its lack of de novo synthesis of sialic acids by expressing a surface-anchored trans-sialidase. This enzyme transfers sialic acid residues from the host's sialylglycoconjugates to the parasite's galactosylglycoconjugates. In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. A major obstacle to understand these events is the difficulty to identify the transferred sialic acid among all those naturally occurring on the cell surface. Here, we report the use of azido-modified unnatural sialic acid to identify those molecules that act as cell surface acceptors of the sialyl residue in the trans-sialidase-catalyzed reaction, which might then be involved in the immune alterations induced. In living parasites, we readily observed the transfer of azido-sialic acid to surface mucins. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. In both leukocyte populations, the main proteins labeled were identified as different CD45 isoforms. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Nevertheless, CD45 remained to be the main acceptor. Mass spectrometry assays allowed us to identify other acceptors, mainly integrins. The findings reported here provide a molecular basis to understand the abnormalities induced in the immune system by the trans-sialidase during T. cruzi infection. |
| PMID: 20354005 [PubMed - indexed for MEDLINE] | |
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| 8. | Medicina (B Aires). 2009;69(4):424-30.[Vectorial and congenital transmission of Tr ypanosoma cruzi in Las Lomitas, Formosa][Article in Spanish] Sosa-Estani S, Dri L, Touris C, Abalde S, Dell'arciprete A, Braunstein J.Centro Nacional de Diagnóstico e Investigación de Endemo-epidemias (CeNDIE), Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) Dr. Carlos G. Malbrán. ssosa@msal.gov.ar AbstractChagas disease, caused by Trypanosoma cruzi, is a major cause of morbidity and mortality in Latin America. The objective of this study was to describe the rate of infestation in four aboriginal communities in Las Lomitas (Great Chaco Region), Formosa, Argentina; the rate of infection in children residing in these communities, in blood donors and in pregnant women who received care at the Hospital Las Lomitas, as well as the rate of congenital infection in children born to women infected during the study period. The rate of infestation of 172 households evaluated in 2006 reached 32%. Prevalence of infection among 445 people was 17.5% and in children under 5 years old it was 8.6%. The rate of infection reached 18.6% in blood donors and 29.1% in pregnant women. The rate of infection among 47 children born to infected women, and living in residences under vectorial surveillance was 17.0%. These infections were considered as congenital. This study showed indexes compatible with active vectorial transmission at the beginning. After vectorial control with insecticides the infestation rate has been reduced to 3.3%. The local health system has introduced high impact procedures of primary and secondary prevention in order to prevent new cases and to treat infected people. |
| PMID: 19770096 [PubMed - indexed for MEDLINE] | |
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