This study aimed to identify putative functional polymorphisms in the IFNGR1 gene, and to determine whether differences in expression of interferon-γ (IFNG) and IFNGR1 at the RNA level are associated with pathogenesis of VL and/or PKDL in Sudan.
As based on their region in the gene, some single nucleotide polymorphisms (SNP) can influence the expression of their corresponding proteins, this study aimed to investigate the association between SNP in the IL-10, IL-12, IFN-γ genes and susceptibility to VL.
Furthermore, stimulation of PBMC isolated from VL patients with rLdcTXN resulted in up-regulation of IL-4 and IL-10 production whereas IL-12 and IFN-γ was significantly down-regulated suggesting a pivotal role of cTXN in provoking the immune suppression during VL.
Dependency of B-1 Cells in the Maintenance of Splenic Interleukin-10 Producing Cells and Impairment of Macrophage Resistance in Visceral Leishmaniasis.
In the primary domestic reservoir of VL, dogs, we define occurrence of both CD4(+) and CD8(+) T cell exhaustion as a significant stepwise loss of Ag-specific proliferation and IFN-γ production, corresponding to increasing VL symptoms.
In comparison with the spleens of the other two patients without visceral leishmaniasis, an increase was observed in the CD4/CD8 ratio and in the number of IL-10- and FoxP3-producing cells, while the number of IL-17-producing cells was lower in the spleen of the patient with visceral leishmaniasis.
The in vitro peptide stimulation of peripheral blood mononuclear cells (PBMC) from cured HLA-A02<sup>+</sup> visceral leishmaniasis (VL) subjects produced significantly higher IFN-γ, IL-2 and IL-12 compared to no peptide control healthy subjects.
Immunization with rLdp45 exerted considerable prophylactic efficacy (∼85%) supported by an increase in mRNA expression of iNOS, IFN-γ, TNF-α and IL-12 and decrease in TGF-β and IL-4, indicating its potential as a vaccine candidate against VL.
We performed combined blockade of IFN-γ and TNF-α in VL splenic biopsies and demonstrated it's impact on number of viable amastigotes and cytokine production.
The data presented here confirm the results of previous reports that polymorphisms at the -819 position of the IL-10 gene can influence susceptibility to VL suggesting that the C/T genotype may be considered as a risk factor for the disease.
The IL-10 production and Foxp3 expression in peripheral blood mononuclear cells from VL subjects were observed regulated significantly (p = 0.0131 and 0.0436 when compared with untreated samples) in presence of an antagonist to LFA-3.
The stimulation of peripheral blood mononuclear cells with r-LdODC up-regulated IL-10 production but not IFN-γ production from CD4(+) T cells in active as well as cured visceral leishmaniasis cases, indicating a pivotal role for r-LdODC in causing strong immune suppression in a susceptible host.
MicroRNA 155 (miR155) promotes CD4<sup>+</sup> Th1 responses and IFN-γ production by targeting suppressor of cytokine signaling-1 (SOCS1) and Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1) and therefore could play a role in the resolution of VL.
This was mediated, at least in part, through IFN-γ-induced activation of STAT3 and expression of IL-10, which suggests that splenic macrophages in VL are conditioned to respond to macrophage activation signals with a counter-regulatory response that is ineffective and even disease-promoting.
The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL.
The protection against VL was associated with increased production of nitric oxide (NO), interferon gamma (IFN-γ), IL-17A, and tumor necrosis factor alpha by splenic cells restimulated <i>ex vivo</i> with <i>L. infantum</i> antigens.
However, lymphocytes from sVL stimulated with SLA had lower percentages of CD4<sup>+</sup> and CD8<sup>+</sup> cells expressing CD69 and CD8<sup>+</sup> cells expressing CD25, with no release of interferon-γ or tumor necrosis factor. sVL subjects had lower percentage of memory cells (CD4<sup>+</sup> CD45RO+), ex vivo, without SLA stimulation than RecVL, LST+, or LST- (<i>P</i> = 0.0022).
Furthermore, stimulation of PBMC isolated from VL patients with rLdcTXN resulted in up-regulation of IL-4 and IL-10 production whereas IL-12 and IFN-γ was significantly down-regulated suggesting a pivotal role of cTXN in provoking the immune suppression during VL.
We performed combined blockade of IFN-γ and TNF-α in VL splenic biopsies and demonstrated it's impact on number of viable amastigotes and cytokine production.