Modulation of the cell-mediated immune response in kala-azar and post-kala-azar dermal leishmaniasis in relation to chemotherapy

Neogy, A.B.; Nandy, Abhishek; Dastidar, B. Ghosh; Chowdhury, A. B.

doi:10.1080/00034983.1988.11812205

Cited by 30 publications

(27 citation statements)

References 10 publications

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“…Patients with kala azar develop immune suppression (47), and the same is true for experimental infection of hamsters (16). As a measure of the cell-mediated immune response, proliferation of splenocytes with leishmanial antigens (SLA) was studied in the hamster model.…”

Section: Resultsmentioning

confidence: 99%

Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells

et al. 2009

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The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stimulating ability and is dependent on the cholesterol content of the membrane. The relationship, if any, between membrane fluidity and defective cell-mediated immunity in visceral leishmaniasis has been investigated. Systemic administration of cholesterol by liposome delivery (cholesterol liposomes) in Leishmania donovaniinfected hamsters was found to cure the infection. Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. Infection led to increases in interleukin-10 (IL-10), transforming growth factor beta, and IL-4 signals and concomitant decreases in gamma interferon (IFN-␥), tumor necrosis factor alpha, and inducible NO synthase signals, which reverted upon cholesterol liposome treatment. The antileishmanial T-cell repertoire, whose expansion appeared to be associated with protection, was presumably type Th1, as shown by enhanced IFN-␥ signals and the predominance of the immunoglobulin G2 isotype. The protected group produced significantly more reactive oxygen species and NO than the infected groups, which culminated in killing of L. donovani parasites. Therefore, cholesterol liposome treatment may be yet another simple strategy to enhance the cell-mediated immune response to L. donovani infection. To our knowledge, this is the first report on the therapeutic effect of cholesterol liposomes in any form of the disease.

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Section: Resultsmentioning

confidence: 99%

Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells

et al. 2009

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“…The specificity of the IGRA was estimated in this study on a valid group of healthy controls recruited in an area where VL and L. donovani transmission are not endemic, but it should be further investigated on more-representative control groups recruited from areas where VL is endemic to evaluate the potential use of this marker for epidemiological studies. The group of cured VL used for sensitivity estimation was clinically well characterized and would seem a valid basis for sensitivity estimation, as cure correlates with cellular immunity (20). The IGRA results can be compared only to the imperfect standard of serology.…”

Section: Discussionmentioning

confidence: 99%

Reassessment of Immune Correlates in Human Visceral Leishmaniasis as Defined by Cytokine Release in Whole Blood

Singh

Gidwani

Kumar

et al. 2012

Clin Vaccine Immunol

106

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ABSTRACTDepressed cell-mediated immunity in human visceral leishmaniasis (VL) (also known as kala-azar), revealed as the inability of peripheral blood mononuclear cells (PBMCs) to respond toLeishmaniaantigen, remains a hallmark of and is thought to underlie the progressive nature of this disease. We recently reported the ability of a whole-blood, gamma interferon (IFN-γ) release assay to detect subclinical infections among healthy individuals living in an area where kala-azar is endemic (Bihar, India) and the surprising result that patients with active VL also secreted significant levels of antigen-specific IFN-γ in this assay. We were interested in ascertaining whether these findings would be true for a larger cohort of subjects and in employing the whole-blood assay to detect additional cytokines that might better correlate with the disease status of infected individuals. We evaluated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin-10 (IL-10) release in 35 patients with active VL, 54 patients with VL who were cured, 27 patients with other diseases, 52 healthy controls who lived in regions where VL or kala-azar is not endemic (NEHCs [for nonendemic healthy controls]), and 147 healthy controls who lived in regions where kala-azar is endemic (EHCs [for endemic healthy controls]). The cellular responses of the EHCs were correlated with their serological antibody titers againstLeishmania donovaniandPhlebotomus argentipessaliva. The whole-blood cells from the majority of both active (80%) and cured (85%) VL patients, as well as 24% of EHCs with presumed subclinical infections, produced significantly elevated levels of IFN-γ. The findings do not support a severe Th1 response defect in kala-azar. Importantly, only the patients with active VL also produced IL-10, which in conjunction with IFN-γ better reflects the immune responses that distinguish individuals with active disease from cured or subclinically infected, immune individuals.

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“…For example, CD40-CD40L interactions enhance IL-12 production, and mice lacking this pathway are susceptible to CL. It has been shown that the neutralization or removal of IL-12 gene in resistant mice makes it susceptible for Leishmania infection and, reconstitution of IL-12p40−/− mice with exogenous IL-12 makes it further protective or resistant [355][356][357]. The capacity of exogenous IL-12 to heal infected mice correlated with powerful effect of IL-12 in suppressing IL-4 transcription and protein production.…”

Section: Immune Response To Leishmania and Its Mechanismmentioning

confidence: 99%

Vaccine candidates for leishmaniasis: A review

Nagill

Kaur

2011

International Immunopharmacology

111

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Modulation of the cell-mediated immune response in kala-azar and post-kala-azar dermal leishmaniasis in relation to chemotherapy

Cited by 30 publications

References 10 publications

Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells

Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells

Reassessment of Immune Correlates in Human Visceral Leishmaniasis as Defined by Cytokine Release in Whole Blood

Vaccine candidates for leishmaniasis: A review

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