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81.
Bimal S Singh SK Sinha S Pandey K Sinha PK Ranjan A Bhattacharya SK Das P 《Experimental parasitology》2008,118(2):238-246
In this study, we investigated whether alteration in the CD2 mediated coordination of an immune response was associated with down regulation of CD4 associated Th1 cell response during Visceral Leishmaniasis (VL). Leishmania donovani (Ld) infection in VL patients markedly reduced expression of CD2 cell surface antigen on CD4+ cells. T-cells of VL patients were mostly in G0/G1 stage of the cell cycle (98.20%) with little or no activity of protein kinase C-alpha (PKC-alpha) isoform. However, pre-incubation with activating anti-CD2 monoclonal antibody (MAb) resulted in a corresponding increase up to 2.52-fold in T-cells of G2/M population supported by both activity and expression of PKC-alpha isoform. Furthermore, we observed that co-incubation of T-cell with anti-CD2 increased the lymphocyte-blast population in patients in whom the CD4 cells became more antigen responsive (CD4+ CD69+ cells). Consistent with these observations, it was shown that 59.3% of CD4 cells from patients responded to Ld by producing IFN-gamma. Even in the culture condition, when the T-cells from patients were depleted of APC, IFN-gamma production was noticed after CD2 activation. On the other hand, IL-4 production became low in the anti-CD2 antibody supplemented peripheral blood mononuclear cells (PBMNCs) culture. These findings imply that infection with L. donovani induces less CD2 on the surface of CD4+ T-cells, which once activated orchestrate the protective IFN-gamma dominant host defense mechanism via PKC-mediated signal transduction and cell cycle. 相似文献
82.
Argueta-Donohué J Carrillo N Valdés-Reyes L Zentella A Aguirre-García M Becker I Gutiérrez-Kobeh L 《Experimental parasitology》2008,120(1):1-9
Dendritic cells (DC) and macrophages (Mφ) are well known as important effectors of the innate immune system and their ability to produce IL-12 indicates that they possess the potential of directing acquired immunity toward a Th1-biased response. Interestingly, the intracellular parasite Leishmania has been shown to selectively suppress Mφ IL-12 production and are DC the principal source of this cytokine. The molecular details of this phenomenon remain enigmatic. In the present study we examined the effect of Leishmania mexicana lipophosphoglycan (LPG) on the production of IL-12, TNF-α, and IL-10 and nuclear translocation of NF-κB. The results show that LPG induced more IL-12 in human DC than in monocytes. This difference was due in part to nuclear translocation of NF-κB, since LPG induced more translocation in DC than in monocytes. These results suggest that Leishmania LPG impairs nuclear translocation of NF-κB in monocytes with the subsequent decrease in IL-12 production. 相似文献
83.
Kavoosi G Ardestani SK Kariminia A Zeinali M Alimohammadian MH 《Experimental parasitology》2008,120(1):62-66
Protozoan parasites of the genus Leishmania secrete a range of proteophosphoglycans (PPG) known to be important for successful colonization of Leishmania in the sandfly and for virulence in the mammalian host. PPGs are a large family of extensively glycosylated proteins with some unusual and unique features. In this study we purified PPG from culture supernatant of Leishmania major metacyclic promastigotes. In discontinuous SDS-PAGE, PPG could not enter the resolving gel but after mild acid hydrolysis several bands resolved. Agarose gel electrophoresis and immunoblot analysis using monoclonal antibody (WIC 79.3) indicated that the PPG preparation consisted of heterogeneous molecules. Compositional analysis showed that the PPG preparation contained 67% glycan, 28% protein and 5% phosphate. Additionally, the effect of PPG on reactive oxygen species (ROS) production and induction of IL-10, IL-12 and IFN-γ secretion by human peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals was investigated. The water-soluble secreted form of PPG at a concentration of 1 μg glycan/ml seems to be a potent inducer of ROS and IL-10 and to a lesser extent of IFN-γ and IL-12. Cytokines and ROS production was decreased in a dose-dependent manner as the concentration of PPG was increased to 100 μg glycan/ml. 相似文献
84.
Natalia Cadaxo Rochael Luize Gon?alves Lima Sandra Maria Pereira de Oliveira Marcello André Barcinski Elvira Maria Saraiva Robson Queiroz Monteiro Lucia Helena Pinto-da-Silva 《Memórias do Instituto Oswaldo Cruz》2013,108(6):679-685
Leishmania parasites expose phosphatidylserine (PS) on their
surface, a process that has been associated with regulation of host''s immune
responses. In this study we demonstrate that PS exposure by metacyclic
promastigotes of Leishmania amazonensis favours blood
coagulation. L. amazonensis accelerates in vitro coagulation of
human plasma. In addition, L. amazonensis supports the assembly
of the prothrombinase complex, thus promoting thrombin formation. This process
was reversed by annexin V which blocks PS binding sites. During blood meal,
Lutzomyia longipalpis sandfly inject saliva in the bite
site, which has a series of pharmacologically active compounds that inhibit
blood coagulation. Since saliva and parasites are co-injected in the host during
natural transmission, we evaluated the anticoagulant properties of sandfly
saliva in counteracting the procoagulant activity of L.
amazonensis . Lu. longipalpis saliva reverses
plasma clotting promoted by promastigotes. It also inhibits thrombin formation
by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS
vesicles or in L. amazonensis . Sandfly saliva inhibits factor
X activation by the intrinsic tenase complex assembled on PC/PS vesicles and
blocks factor Xa catalytic activity. Altogether our results show that metacyclic
promastigotes of L. amazonensis are procoagulant due to PS
exposure. Notably, this effect is efficiently counteracted by sandfly
saliva. 相似文献
85.
S. ESSEGHIR P. D. READY R. BEN-ISMAIL 《Biological journal of the Linnean Society. Linnean Society of London》2000,70(2):189-219
The phylogcny and mode of speciation of Mediterranean Phlebotomus of the subgenus Larroussius were inferred by comparative sequence analyses of a fragment of mitochondrial DNA (Cytochrome b) and of a nuclear gene (Elongation factor alpha). The molecular phytogenies were congruent basally, where their clades matched the species complexes defined by a few genitalic characters of each sex. Reticulate evolution was suggested for the most derived species complex [Phlebotomus perniciosus): the molecular phytogenies were incongruent, and mitochondrial-marker distribution was consistent with introgressive hybridizations not between sister species but between species whose ranges now overlap or abut. By considering the molecular phytogenies, the mitochondrial molecular clock and the ecological niches of the species, as well as the historical biogeography and palaeoecology of the Mediterranean subregion, we propose that the derived lineages arose from a sequential series of speciation events associated with habitat shifts promoted by progressive aridification. This 'taxon pulse'-like speciation occurred in the Pliocene, later than previously proposed in a vicariance hypothesis that invoked only tectonic events, but too early for Pleistocene Ice-age refugia to have played any role other than the isolation of geographical races. Speciation occurred before the proposed divergence of members of the Leishmania donovani complex and this helped to rule out any vector-parasite co-speciation or co-cladogenesis. 相似文献
86.
Maritza Padrón-Nieves 《Experimental parasitology》2009,121(4):331-337
A source of chemotherapeutic failure in anti-infective therapies is the active movement of drugs across membranes, through ATP-binding cassette (ABC) transporters. In fact, simultaneous administration of therapeutic drugs with ABC transporter blockers has been invoked to be the way to actively prevent the emergence of drug resistance. Herein, we demonstrate that glucantime’s efficacy in decreasing the infection rate of Leishmania-infected macrophages is strongly enhanced when used in combination with glibenclamide, a specific blocker of ABC transporters. Intracellular ABC transporters mediate glucantime sequestration in intracellular organelles. Their selective inhibition may effectively increase the cytoplasmic concentration of glucantime and its leishmanicidal activity. Our results reveal for the first time that glibenclamide targets in Leishmania major a compartment associated with a multivesicular system that is simultaneously labeled by the acidic marker LysoTracker-red and may represent the organelle where antimonials are sequestered. These results constitute a proof of concept that conclusively demonstrates the potential value that combination therapy with an ABC transporter blocker may have for leishmaniasis therapy. 相似文献
87.
Sayan Chowdhury Rupkatha Mukhopadhyay Sourav Saha Amartya Mishra Souvik Sengupta Syamal Roy Hemanta K. Majumder 《The Journal of biological chemistry》2014,289(23):16129-16147
In parasites, ATP-binding cassette (ABC) transporters represent an important family of proteins related to drug resistance and other biological activities. Resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries, and in many instances, it is due to overexpressed ABC efflux pumps. Progressively adapted baicalein (BLN)-resistant parasites (pB25R) show overexpression of a novel ABC transporter, which was classified as ABCC2 or Leishmania donovani multidrug resistance protein 2 (LdMRP2). The protein is primarily localized in the flagellar pocket region and in internal vesicles. Overexpressed LdABCC2 confers substantial BLN resistance to the parasites by rapid drug efflux. The BLN-resistant promastigotes when transformed into amastigotes in macrophage cells cannot be cured by treatment of macrophages with BLN. Amastigote resistance is concomitant with the overexpression of macrophage MRP2 transporter. Reporter analysis and site-directed mutagenesis assays demonstrated that antioxidant response element 1 is activated upon infection. The expression of this phase II detoxifying gene is regulated by NFE2-related factor 2 (Nrf2)-mediated antioxidant response element activation. In view of the fact that the signaling pathway of phosphoinositol 3-kinase controls microfilament rearrangement and translocation of actin-associated proteins, the current study correlates with the intricate pathway of phosphoinositol 3-kinase-mediated nuclear translocation of Nrf2, which activates MRP2 expression in macrophages upon infection by the parasites. In contrast, phalloidin, an agent that prevents depolymerization of actin filaments, inhibits Nrf2 translocation and Mrp2 gene activation by pB25R infection. Taken together, these results provide insight into the mechanisms by which resistant clinical isolates of L. donovani induce intracellular events relevant to drug resistance. 相似文献
88.
ABSTRACT Earlier studies showed that Leishmania major promastigotes are sensitive to osmotic conditions. A reduction in osmolality caused the cells to shorten and to rapidly release most of their large internal pool of alanine. In this study some effects of hyper-osmotic stress were examined. an increase in osmolality of the culture medium from 308 to 625 mOsm/kg caused only a small decrease in growth rate. When cells grown in the usual culture medium (308 mOsm/kg) were washed, resuspended in iso-osmotic buffer, and subjected to acute hyper-osmotic stress by addition of mannitol, the alanine content increased even in the absence of exogenous substrate. Promastigotes, depleted of alanine by a 5-min exposure to hypo-osmotic conditions, also synthesized alanine when resuspended in iso-osmotic buffer. Washed cells resuspended in iso-osmotic buffer consume their internal pool of alanine under aerobic conditions, Rates of consumption decreased on addition of mannitol, becoming zero at about 440 mOsm/kg. At higher osmolalities, alanine synthesis occurred. to estimate whether proteolysis could account for alanine synthesis in the absence of exogenous substrate, cells that had been grown with [1-14 C]leucine were washed and resuspended under hypo-, iso-, and hyper-osmotic conditions and the amounts of 14 CO2 and 14 C-labelled peptides released in 1 h were measured. Little proteolysis occurred under these conditions, but the possibility that proteolysis was the source of the alanine increase, observed in response to hyper-osmotic stress, cannot be ruled out. 相似文献
89.
B. ALEXANDER M. C. USMA H. CADENA B. L. QUESADA Y. SOLARTE W. ROA J. MONTOYA C. JARAMILLO B. L. TRAVI 《Medical and veterinary entomology》1995,9(3):273-278
Abstract. A survey was made of the phlebotomine sandfly fauna of La Guaira, a village with coffee plantations near Cali, Colombia, from which cases of American cutaneous leishmaniasis had been reported due to Leishmania (Viannia) panamensis and Le. ( V. ) braziliensis. Among six species of sandfly collected on human bait, Lutzomyia youngi was most important in terms of biting nuisance. Lu. columbiana, Lu. lichyi and Lu. scorzai as well as Lu. youngi adults occurred throughout the year. Sandfly man-biting activity occurred throughout the night and was highest within 2 h of sunset. Despite its abundance in nocturnal samples, Lu. youngi was rarely taken in diurnal resting site collections. In contrast, Lu. lichyi was collected on tree-trunks during the day in large numbers and was the only species biting in daylight. The implications of these and other findings for leishmaniasis control measures in La Guaira are considered. 相似文献
90.
Masoud Doroodgar Mahdi Delavari Moein Doroodgar Ali Abbasi Ali Akbar Taherian Abbas Doroodgar 《The Korean journal of parasitology》2016,54(1):9-14
Tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. The current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. Therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of Leishmania major Iranian strain were evaluated in vitro. Promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and 50 μg/ml) and time periods (24, 48, and 72 hr) of tamoxifen. After tamoxifen treatment, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 biphenyl tetrazolium bromide assay) was used to determine the percentage of live parasites and Graph Pad Prism software to calculate IC50. Flow cytometry was applied to investigate the induction of tamoxifen-induced apoptosis in promastigotes. The half maximal inhibitory concentration (IC50) of tamoxifen on promastigotes was 2.6 μg/ml after 24 hr treatment. Flow cytometry analysis showed that tamoxifen induced early and late apoptosis in Leishmania promastigotes. While after 48 hr in control group the apoptosis was 2.0%, the 50 µg/L concentration of tamoxifen increased it to 59.7%. Based on the in vitro antileishmanial effect, tamoxifen might be used for leishmaniasis treatment; however, further researches on in vivo effects of tamoxifen in animal models are needed. 相似文献