Wednesday, April 22, 2009

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 -8 of 8

1: PLoS Pathog. 2009 Apr;5(4):e1000381. Epub 2009 Apr 17.

A Novel Role for Stat1 in Phagosome Acidification and Natural Host Resistance to Intracellular Infection by Leishmania major.

Späth GF, Schlesinger P, Schreiber R, Beverley SM.

Department of Molecular Microbiology, Washington University Medical School, St. Louis, Missouri, United States of America.

Intracellular parasites of the genus Leishmania generate severe diseases in humans, which are associated with a failure of the infected host to induce a protective interferon gamma (IFNgamma)-mediated immune response. We tested the role of the JAK/STAT1 signaling pathway in Leishmania pathogenesis by utilizing knockout mice lacking the signal transducer and activator of transcription 1 (Stat1) and derived macrophages. Unexpectedly, infection of Stat1-deficient macrophages in vitro with promastigotes from Leishmania major and attenuated LPG1 knockout mutants (lpg(-)) specifically lacking lipophosphoglycan (LPG) resulted in a twofold increased intracellular growth, which was independent of IFNgamma and associated with a substantial increase in phagosomal pH. Phagosomes in Stat1-/- macrophages showed normal maturation as judged by the accumulation of the lysosomal marker protein rab7, and provided normal vATPase activity, but were defective in the anion conductive pathway required for full vesicular acidification. Our results suggest a role of acidic pH in the control of intracellular Leishmania growth early during infection and identify for the first time an unexpected role of Stat1 in natural anti-microbial resistance independent from its function as IFNgamma-induced signal transducer. This novel Stat1 function may have important implications to studies of other pathogens, as the acidic phagolysosomal pH plays an important role in antigen processing and the uncoating process of many viruses.

PMID: 19381261 [PubMed - in process]

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2: J Immunol. 2009 May 1;182(9):5702-11.

IL-7 Receptor Expression Provides the Potential for Long-Term Survival of Both CD62Lhigh Central Memory T Cells and Th1 Effector Cells during Leishmania major Infection.

Colpitts SL, Dalton NM, Scott P.

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Infection with the intracellular protozoan parasite Leishmania major induces a state of concomitant immunity wherein secondary immunity is dependent upon the persistence of the original pathogen. Our laboratory has described two populations of Leishmania-induced CD4(+) T cells that contribute to immunity: CD62L(high) central memory T (T(CM)) cells and CD62L(low) effector T cells. To determine whether the prosurvival cytokine IL-7 contributes to maintaining these T cells, we examined expression of the IL7R on CD4(+) T cells activated during L. major infection. We found that T(CM) cells present in chronically infected mice expressed high levels of the IL7R. However, in addition to the expression of the IL7R by T(CM) cells, CD62L(low) cells responding to L. major infection expressed the IL7R. Additional experiments revealed that a large percentage of the IL7R(high)CD62L(low) cells were Th1 cells, based on transcription at the IFN-gamma locus and up-regulation of the Th1-promoting transcription factor T-bet. The up-regulation of T-bet did not prevent IL7R expression by L. major-responding CD4(+) T cells, nor did the absence of T-bet result in increased IL7R expression. Finally, blockade of IL7R signaling decreased the number of T-bet(+)CD4(+) T cells, reduced IFN-gamma production, and inhibited delayed-type hypersensitivity responses in immune mice challenged with L. major, indicating that IL7R signaling contributes to the maintenance of Th1 effector cells. Thus, both T(CM) and Th1 effector cells can express the IL7R during chronic L. major infection, which provides a potential means for their long-term survival in addition to the presence of persisting parasites.

PMID: 19380817 [PubMed - in process]

3: J Leukoc Biol. 2009 Apr 20. [Epub ahead of print]

A new function of the Fas-FasL pathway in macrophage activation.

Chakour R, Allenbach C, Desgranges F, Charmoy M, Mauel J, Garcia I, Launois P, Louis J, Tacchini-Cottier F.

*World Health Organization Immunology Research and Training Centre andDepartment of Biochemistry, University of Lausanne, Epalinges, Switzerland;Department of Parasitology, Institut Pasteur, Paris, France; andDepartment of Pathology, University of Geneva, Switzerland.

Upon infection with the protozoan parasite Leishmania major, susceptible BALB/c mice develop unhealing lesions associated with the maturation of CD4(+ )Th2 cells secreting IL-4. In contrast, resistant C57BL/6 mice heal their lesions, because of expansion and secretion of IFN-gamma of CD4(+) Th1 cells. The Fas-FasL pathway, although not involved in Th cell differentiation, was reported to be necessary for complete resolution of lesions. We investigate here the role of IFN-gamma and IL-4 on Fas-FasL nonapoptotic signaling events leading to the modulation of macrophage activation. We show that addition of FasL and IFN-gamma to BMMø led to their increased activation, as reflected by enhanced secretion of TNF, IL-6, NO, and the induction of their microbicidal activity, resulting in the killing of intracellular L. major. In contrast, the presence of IL-4 decreased the synergy of IFN-gamma/FasL significantly on macrophage activation and the killing of intracellular L. major. These results show that FasL synergizes with IFN-gamma to activate macrophages and that the tight regulation by IFN-gamma and/or IL-4 of the nonapoptotic signaling events triggered by the Fas-FasL pathway affects significantly the activation of macrophages to a microbicidal state and may thus contribute to the pathogenesis of L. major infection.

PMID: 19380712 [PubMed - as supplied by publisher]

4: Int J Biochem Cell Biol. 2009 Apr 17. [Epub ahead of print]

Particularities of Mitochondrial Structure in Parasitic Protozoa (Apicomplexa and Kinetoplastida).

de Souza W, Attias M, Rodrigues JC.

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, Ilha do Fundão, 21941-902, Rio de Janeiro-RJ, Brasil; Diretoria de Programas, Instituto Nacional de Metrologia e Qualidade Industrial-INMETRO.

Without mitochondria, eukaryotic cells would depend entirely on anaerobic glycolysis for ATP generation. This also holds true for Protists, both free-living and parasitic. Parasitic Protists include agents of human and animal diseases that have a huge impact on world populations. In the phylum Apicomplexa, several species of Plasmodium cause malaria, whereas Toxoplasma gondii is a cosmopolite parasite found on all continents. Flagellates of the order Kinetoplastida include the genera Leishmania and Trypanosoma causative agents of human leishmaniasis and (depending on the species) African trypanosomiasis and Chagas disease. Although clearly distinct in many aspects, the members of these two groups bear a single and usually well developed mitochondrion. The single mitochondrion of Apicomplexa has a dense matrix and many cristae with a circular profile. The organelle is even more peculiar in the order kinetoplastida, exhibiting a condensed network of DNA at a specific position, always close to the flagellar basal body. This arrangement is known as Kinetoplast and the name of the Order derived from it. Kinetoplastids also bear glycosomes, peroxisomes that concentrate enzymes of the glycolytic cycle. Mitochondrial volume and activity is maximum when glycosomal is low and vice versa. In both Apicomplexa and Trypanosomatids, mitochondria show particularities that are absent in other eukaryotic organisms. These peculiar features make them an attractive target for therapeutic drugs for the diseases they cause.

PMID: 19379828 [PubMed - as supplied by publisher]

5: Vet Res. 2009 Apr 21;40(2):38. [Epub ahead of print]

Perpetuation of Leishmania: some novel insight into elegant developmental programs.

Milon G.

Leishmania spp. are polarized single-celled eukaryotic parasites, the perpetuation of which relies on two other organisms they use as hosts. One of the Leishmania host organisms is a blood-feeding female sand fly, the second host being a mammal that acts as a blood source for the female sand fly. Leishmania-hosting sand flies transmit the metacyclic promastigote developmental stage to the mammal skin. While many mammals are known to act as sand fly blood sources, only some of these mammals are/will be used as Leishmania hosts. This host status means that skin as well as skin-distant tissues- and cell lineages (mononuclear phagocytes and fibroblasts) of these mammals are rapidly and continuously remodelled as niches where Leishmania will deploy its developmental programs: it is noteworthy that without the deployment of the developmental program underlying Leishmania transmission from the mammal to the blood-searching and blood-feeding sand flies, the perpetuation of Leishmania will be suspended. While post genomic approaches are providing insight about some features of Leishmania major, L. infantum/chagasi and L. braziliensis, such approaches are not yet available for the natural hosts (wild rodents, wild sand flies) these Leishmania species use as hosts.

PMID: 19379663 [PubMed - as supplied by publisher]

6: Dermatol Online J. 2009 Mar 15;15(3):10.

Rhinophymous leishmaniasis: A new variant.

Ul Bari A, Ejaz A.

Consultant Dermatologist, Combined Military Hospital, Peshawar, Pakistan.

Cutaneous leishmaniasis is known for its wide clinical spectrum. The nose is one of the usual sites where the disease can present in many forms, such as psoriasiform plaques, furunculoid nodules, lupoid plaques, and erysipeloid or mucocutaneous types. We present a new morphology, i.e. rhinophyma-like plaque in an elderly male patient who presented with a large infiltrated plaque involving his nose and the adjoining area of his upper lip. It appeared to be rhinophyma of the nose but was diagnosed as cutaneous leishmaniasis after the demonstration of leishmania parasites in a skin smear preparation; he was treated satisfactorily with antimonials.

PMID: 19379654 [PubMed - in process]

7: Turk J Pediatr. 2009 Jan-Feb;51(1):1-5.

Visceral childhood leishmaniasis in southern Turkey: experience of twenty years.

Dursun O, Erişir S, Yeşilipek A.

Division of Intensive Care, Department of Pediatrics, Akdeniz University Faculty of Medicine, Antalya, Turkey.

One hundred and one children with visceral leishmaniasis (VL) who admitted to Akdeniz University Hospital during a 20-year period were analyzed. Median age of the patients was 3 years (range: 5.5 months-13 years). The most common symptoms at presentation were fever, pallor and abdominal distension. Splenomegaly was found in all of the patients while hepatomegaly was present in 98%. Anemia (96%), leukopenia (74%) and thrombocytopenia (56%) were the main laboratory abnormalities. Thirty-three (33%) of the patients were pancytopenic on admission. Bone marrow smear was positive for leishmania in 91% of the patients. Seventy-four patients were treated with antimony +/- pentamidine and 27 with amphotericin B. Three of our patients died because of secondary infections and hemorrhage. Relapse was observed in two patients. No patient showed post kala-azar dermal leishmaniasis findings. We conclude that VL should be considered in patients with prolonged fever, hepatosplenomegaly and cytopenia who live in an endemic region. Amphotericin B is a therapeutic agent as effective as pentavalent antimony compounds and could be preferred.

PMID: 19378883 [PubMed - in process]

8: Zh Obshch Biol. 2009 Jan-Feb;70(1):78-93.LinkOut

[Spatial structure of communities of heterotrophic flagellates from a sphagnum bog]

[Article in Russian]

Tikhonenkov DV, Mazeĭ IuA.

Spatial distribution pattern of heterotrophic flagellates within a macroscopically homogenous sphagnum parcel of a transitional bog in the southern taiga was studied. Under investigation was horizontal pattern at different scales (1 cm, 10 cm, 1 m, 10 m) and the vertical heterogeneity of the community in the sphagnum quagmire. 105 species and forms of heterotrophic flagellates were revealed. Predominating were euglenids, less abundant are kynetoplastids and cercomonads. The most numerous appeared to be Cryptomonas sp., Heteromita minima, Goniomonas truncata, Protaspis simplex, Bodo designis, B. saltans, Phyllomitus apiculatus, Paraphysomonas sp., Petalomonas minuta. More abundant species were characterized by less patchy distribution than less abundant. At a smaller scale, the community was formed by the species with different degree of patchiness while at larger scales, all the species possess nearly the same distribution pattern. The same number of samples of equal sizes revealed nearly the same species numbers independently of distances between the sample sites, as the samples at each scale differ from each other nearly at the same magnitude. An averaged size of the species aggregations in the community is as large as several centimeters. Such a scale is probably a characteristic size (minimum area) of the community of the sphagnum dwelling heterotrophic flagellates. Rather low environmental heterogeneity within the sphagnum quagmire leads to significant homogeneity of the community at larger scales. Vertical differentiation of the heterotrophic flagellate community within that quagmire appeared to be very unstable with the time. The same species are characterized by different preferences to the depths at different spatial-temporal loci. Specific vertical distributions and community patterns are formed under different local conditions.

PMID: 19326857 [PubMed - indexed for MEDLINE]

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