Disease relevance of Leishmaniasis

• Both antigens were effective in inducing the production of IFN-gamma from T cell lines from both leishmaniasis and Chagas' disease patients [1].
• In this study, we tested the ability of a recombinant adenovirus vector-expressing IL-12 to skew the immune response in a Th1 direction and prevent leishmaniasis in susceptible mice [2].
• Anti-IL-9 vaccination showed protective effects, because it enabled L. major-infected nonhealer BALB/c mice to better resist to leishmaniasis with doubling the time span until pathological disease progression occurred [3].
• We report the crystal structures of glycosomal fructose-1,6-bisphosphate aldolase from two major tropical pathogens, Trypanosoma brucei and Leishmania mexicana, the causative agents of African sleeping sickness and one form of leishmaniasis, respectively [4].
• In addition, recombinant TSA protein elicited in vitro proliferative responses from peripheral blood mononuclear cells of human leishmaniasis patients and significant TSA protein-specific antibody titers were detected in sera of both cutaneous-leishmaniasis and visceral-leishmaniasis patients [5].

High impact information on Leishmaniasis

• In leishmaniasis, protection requires leishmanial-specific CD4+ T helper (TH) cells [6].
• IRF-1(-/-) mice showed dramatically exacerbated Leishmaniasis [7].
• Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis [8].
• Finally, combined CD4(+) depletion and IL-4 neutralization were curative, indicating that neither increased parasite burden nor altered accessory cell function independently biased towards Th2 reconstitution in advanced leishmaniasis [9].
• Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide [10].

Chemical compound and disease context of Leishmaniasis

• Hepatotoxicity of sodium stibogluconate in leishmaniasis [11].
• Co-trimoxazole for systemic leishmaniasis [12].
• Pentostam, a Sb(V)-containing drug that is one of the first-line therapeutic agents for treatment of leishmaniasis, inhibited uptake after reaction with GSH [13].
• Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs [14].
• The alkylphosphocholine class of drugs, including edelfosine and miltefosine, has recently shown promise in the treatment of protozoal and fungal diseases, most notably, leishmaniasis [15].

Biological context of Leishmaniasis

• We conclude that immunostimulatory DNA sequences likely exert systemic effects via IL-12 and IFN-gamma-dependent mechanisms and hold considerable promise as both vaccine adjuvants and potential therapeutic agents in the prevention and treatment of leishmaniasis [16].
• Here, we show that IRF4 directly regulates Th cell differentiation in vitro and in vivo during murine leishmaniasis [17].
• Modulation of interferon-gamma-induced macrophage activation by phosphotyrosine phosphatases inhibition. Effect on murine Leishmaniasis progression [18].
• Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products [19].
• These findings demonstrate that IL-12 produced in vivo is necessary for both the emergence of IFN-gamma producing cells and the down-regulation of Th2 cell responses during murine leishmaniasis [20].

Anatomical context of Leishmaniasis

• Because interleukin 12 (IL-12) has potent T cell growth and interferon gamma (IFN-gamma) stimulatory effects, we studied its effect on CD4+ T cell differentiation during murine leishmaniasis [21].
• We sought to restore protective immunity in advanced leishmaniasis by depletion of Th2-biased CD4(+) populations and by cytokine-directed reconstitution of Th1 cellular responses during lymphocyte recovery [9].
• Together, these data indicate that the stimulation of NK cells, through the production of IFN-gamma, plays an important role in initiating Th1 cell differentiation in leishmaniasis and in controlling early resistance to L. major [22].
• We used the model of murine leishmaniasis to evaluate the signals enabling Ag-pulsed dendritic cells (DC) to prime a protective Th1 response in vivo [23].
• The interleukin (IL)-4 driven, polarized T-helper 2 cell (Th2) response that controls non-healing infection with Leishmania major in BALB/c mice has long been embraced as the underlying principle with which to consider the pathogenesis of non-healing and systemic forms of leishmaniasis in humans [24].

Gene context of Leishmaniasis

• Recombinant LeIF (rLeIF) downregulated both IL-10 mRNA in the "resting" PBMC of leishmaniasis patients and LPS-induced IL-10 production by patient PBMC. rLeIF also stimulated the production of IL-12 in cultured PBMC from both patients and uninfected individuals [25].
• In the chronic and destructive mucocutaneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL-4 mRNA in lesions [26].
• TGF-beta has also been recognized as an important immunoregulator in murine leishmaniasis, for which it increases susceptibility to disease [27].
• Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling [28].
• CD4(+) Th1 cells were the main source of IFN-gamma and TNF-alpha production in mucosal leishmaniasis patients [29].

Analytical, diagnostic and therapeutic context of Leishmaniasis

• We have, therefore, demonstrated the feasibility of oral vaccination against leishmaniasis and that the oral route of antigen delivery via the heterologous carrier may preferentially induce Th1 subsets of CD4+ cells [30].
• The prevalence of anti-gp63 antibody in sera of leishmaniasis patients was evaluated by ELISA [31].
• Pentavalent antimony is the drug of choice for leishmaniasis chemotherapy; amphotericin B (AmB) is active but is rarely used, because of drug toxicity [32].
• Because leishmaniasis is accompanied by immunosuppression, immunostimulation by interferon (IFN)-gamma was evaluated to act synergistically with mannosylated liposomal doxorubicin therapy [33].
• The remarkable protection induced by LmSTI1 and TSA in an animal model that is evolutionarily close to humans qualifies this antigen combination as a promising candidate subunit vaccine against human leishmaniasis [34].

References