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Donovani Infection (donovani + infection)
Selected AbstractsLeishmania donovani -induced expression of signal regulatory protein , on Kupffer cells enhances hepatic invariant NKT-cell activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010Lynette Beattie Abstract Signal regulatory protein , (SIRP,) and its cognate ligand CD47 have been documented to have a broad range of cellular functions in development and immunity. Here, we investigated the role of SIRP,,CD47 signalling in invariant NKT (iNKT) cell responses. We found that CD47 was required for the optimal production of IFN-, from splenic iNKT cells following exposure to the ,GalCer analogue PBS-57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRP, was undetectable in the liver of uninfected mice, the hepatic iNKT-cell response to infection was also impaired in CD47,/, mice. However, we found that SIRP, was rapidly induced on Kupffer cells following L. donovani infection, via a mechanism involving G-protein-coupled receptors. Thus, we describe a novel amplification pathway affecting cytokine production by hepatic iNKT cells, which may facilitate the breakdown of hepatic tolerance after infection. [source] The fate of heterologous CD4+ T,cells during Leishmania donovani infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005Rosalind Polley Abstract Little is currently understood about the consequences of chronic parasitic infection for the fate of memory CD4+ T,cells that recognize heterologous antigens, e.g. resulting from prior infections or vaccination. Here, we address how Leishmania donovani infection affected the fate of non-cross-reactive (OVA)-specific memory CD4+ T,cells. DO11 cells were adoptively transferred into naive recipient mice, which were then immunized to generate memory DO11 cells. After 6,weeks, mice were infected with L. donovani and the fate of DO11 cells was determined. L. donovani infection stimulated an approximately threefold expansion in the total number of CD4+ T,cells and DO11 cells, compared to that observed in uninfected mice. DO11 T,cells were more actively dividing in infected mice, as judged by 5-bromo-2, deoxyuridine labeling, whereas their rate of apoptosis in control and infected mice was identical. Both CD45RBhiCD44lo naive T,cells and to a greater extent CD45RBloCD44hi memory DO11 cells increased in number in the spleens of infected mice, whereas no changes occurred to DO11 cell number or phenotype in the draining lymph nodes. These data indicate that heterologous CD4+ T,cells may actively divide during chronic infectious diseases, with important implications for how chronic infection may impact on heterologous immunity. [source] Drug targeting by macromolecules without recognition unit?JOURNAL OF MOLECULAR RECOGNITION, Issue 5 2003Ferenc Hudecz Abstract his review will summarize available information on the ability of macromolecular conjugates containing no specific recognition motifs to deliver anthracyclines (daunomycin, adriamycin) or methotrexate to target cells such as tumour cells or macrophages. Conjugates with natural (proteins, DNA, carbohydrates) and synthetic macromolecules (linear and branched chain poly-,-amino acids, non-biodegradable DIVEMA, HPMA etc.) will be reviewed. Experimental data from several laboratories indicate that these conjugates are taken up by cells mainly by fluid-phase or adsorptive endocytosis. It is believed that these processes do not involve ,specific receptors'. Two examples of methotrexate and daunomycin conjugates will be discussed to show the effect of the chemical structure of branched chain polypeptides on the uptake and antitumour or antiparasitic (Leishmania donovani infection) efficacy of conjugates. Copyright © 2003 John Wiley & Sons, Ltd. [source] Leishmania donovani infection down-regulates TLR2-stimulated IL-12p40 and activates IL-10 in cells of macrophage/monocytic lineage by modulating MAPK pathways through a contact-dependent mechanismCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2008Dinesh Chandra Summary The failure of Leishmania, an intracellular pathogen, to stimulate a pro-inflammatory response following entry into macrophages has been well reported. This occurs in spite of the fact that ligands for the toll-like receptors (TLR) have been recently shown on the parasite surface and their role in disease protection well documented. The outcome of infection in leishmaniasis is determined by the Th1 versus Th2 nature of the effector response and the generation of IL-12 and IL-10 by the infected macrophages is important for this decision. We evaluated the effect of L. donovani infection of monocytes (cell line THP-1, and monocytes derived from human peripheral blood) on Pam3cys (TLR2 ligand) and lipopolysaccharide (TLR4 ligand) stimulated production of IL-12p40 and IL-10. L. donovani infection caused suppression of TLR2 and TLR4-stimulated IL-12p40, with an increase in IL-10 production. Parasites also modulated the TLR2-stimulated mitogen-activated protein kinase (MAPK) pathway by suppressing MAPK P38 phosphorylation and activating extracellular regulated kinase (ERK)1/2 phosphorylation. These effects could be reversed either by using a MAPK P38 activator, anisomycin, or ERK1/2 inhibitor, U0126. L. donovani caused modulation of TLR2-stimulated MAPK pathways in a contact-dependent mechanism. In addition parasite structural integrity but not viability was required for suppression of TLR2-stimulated IL-12p40 and activation of IL-10. These observations suggest that L. donovani has evolved survival strategies that subvert the pro-inflammatory response generated through TLRs. [source] | ||||||||||