Efficacy against VL was mediated by a CD4<sup>+</sup>TNF-α T lymphocyte response against the NH36-F3 domain, while against tegumentary leishmaniasis (TL) a CD8<sup>+</sup> T lymphocyte response to F1 was also required.
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).
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.
Leptin-induced IFN-γ, IL-2, and TNF-α cytokines in the culture supernatant of splenocytes upon soluble leishmanial antigen (SLA) stimulation and significantly up-regulates serum IgG2a titers, which help to generate Th1 immune response in VL.
Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow.
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.
Analyses showed that the distribution of TNFA RFLP alleles (TNF1 and TNF2) and the TNF MSM alleles (TNFa1 to TNFa15) differed between individuals with VL and those with DTH+ phenotypes.
Thus, an aberrant activation of the TNF system with possible negative immunological and virological consequences is present in HIV-1-infected patients with VL.