scholarly journals Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10–Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani

2018 ◽  
Vol 201 (11) ◽  
pp. 3362-3372 ◽  
Author(s):  
Patrick T. Bunn ◽  
Marcela Montes de Oca ◽  
Fabian de Labastida Rivera ◽  
Rajiv Kumar ◽  
Susanna S. Ng ◽  
...  
Hepatology ◽  
2015 ◽  
Vol 63 (2) ◽  
pp. 620-632 ◽  
Author(s):  
Forough Khadem ◽  
Xiaoling Gao ◽  
Zhirong Mou ◽  
Ping Jia ◽  
Hesamaldin Movassagh ◽  
...  

2019 ◽  
Vol 220 (1) ◽  
pp. 163-173 ◽  
Author(s):  
Shashi Bhushan Chauhan ◽  
Rebecca Faleiro ◽  
Rajiv Kumar ◽  
Susanna Ng ◽  
Bhawana Singh ◽  
...  

Abstract Control of visceral leishmaniasis (VL) caused by Leishmania donovani requires interferon-γ production by CD4+ T cells. In VL patients, antiparasitic CD4+ T-cell responses are ineffective for unknown reasons. In this study, we measured the expression of genes associated with various immune functions in these cells from VL patients and compared them to CD4+ T cells from the same patients after drug treatment and from endemic controls. We found reduced GATA3, RORC, and FOXP3 gene expression in CD4+ T cells of VL patients, associated with reduced Th2, Th17, and FOXP3+CD4+ T regulatory cell frequencies in VL patient blood. Interleukin 2 (IL-2) was an important upstream regulator of CD4+ T cells from VL patients, and functional studies demonstrated the therapeutic potential of IL-2 for improving antiparasitic immunity. Together, these results provide new insights into the characteristics of CD4+ T cells from VL patients that can be used to improve antiparasitic immune responses.


2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Himanshu Kaushal ◽  
Rachel Bras-Gonçalves ◽  
Narender Singh Negi ◽  
Jean-Loup Lemesre ◽  
Gérard Papierok ◽  
...  

1998 ◽  
Vol 66 (3) ◽  
pp. 1233-1236 ◽  
Author(s):  
Virmondes Rodrigues ◽  
João Santana da Silva ◽  
Antonio Campos-Neto

ABSTRACT Hamsters infected with Leishmania donovani develop a disease similar to human kala-azar. They present hypergammaglobulinemia, and their T cells do not respond to parasite antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) fromL. donovani-infected hamsters produce high levels of the inhibitory cytokine transforming growth factor β (TGF-β). Immunohistochemical studies with an anti-TGF-β monoclonal antibody (MAb) showed that this cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of TGF-β are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite antigen or lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens ofL. donovani-infected hamsters caused profound inhibition of the in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inhibition was totally abrogated by the anti-TGF-β MAb. These results suggest that the immunosuppression observed in visceral leishmaniasis is, at least in part, due to the abundant production of TGF-β during the course of the infection.


Homeopathy ◽  
2020 ◽  
Vol 109 (04) ◽  
pp. 213-223
Author(s):  
Jyoti Joshi ◽  
Chetna Bandral ◽  
Raj Kumar Manchanda ◽  
Anil Khurana ◽  
Debadatta Nayak ◽  
...  

Abstract Background Leishmaniasis is one of several neglected tropical diseases that warrant serious attention. A disease of socio-economically poor people, it demands safer and cheaper drugs that help to overcome the limitations faced by the existing anti-leishmanials. Complementary or traditional medicines might be a good option, with an added advantage that resistance may not develop against these drugs. Thus, the present investigation was performed to evaluate the anti-leishmanial efficacy of an ultra-diluted homeopathic medicine (Iodium 30c) in experimental visceral leishmaniasis (VL). Methods Compliant with strict ethical standards in animal experimentation, the study was performed in-vivo in inbred BALB/c mice which were injected intravenously with 1 × 107 promastigotes of Leishmania donovani before (therapeutic) or after (prophylactic) treatment with Iodium 30c for 30 days. In other groups of mice (n = 6 per group), amphotericin B served as positive control, infected animals as the disease control, while the naïve controls included normal animals; animals receiving only Iodium 30c or Alcohol 30c served as sham controls. The anti-leishmanial efficacy was assessed by determining the hepatic parasite load and analysing percentages of CD4+ and CD8+ T cells. Biochemical analysis and histological studies were performed to check any toxicities. Results Iodium-treated animals showed a significantly reduced parasite load (to 1503 ± 39 Leishman Donovan Units, LDU) as compared with the infected controls (4489 ± 256 LDU) (p < 0.05): thus, the mean therapeutic efficacy of Iodium 30c was 66.5%. In addition, the population of CD4+ and CD8+ T cells was significantly increased (p < 0.05) after treatment. No toxicity was observed, as evidenced from biochemical and histopathological studies of the liver and kidneys. Efficacy of Iodium 30c prophylaxis was 58.3%, while the therapeutic efficacy of amphotericin B was 85.9%. Conclusion This original study has shown that Iodium 30c had significant impact in controlling parasite replication in experimental VL, though the effect was less than that using standard pharmaceutical treatment.


2012 ◽  
Vol 6 (8) ◽  
pp. e1798 ◽  
Author(s):  
Saruda Tiwananthagorn ◽  
Kazuya Iwabuchi ◽  
Manabu Ato ◽  
Tatsuya Sakurai ◽  
Hirotomo Kato ◽  
...  

2007 ◽  
Vol 204 (4) ◽  
pp. 805-817 ◽  
Author(s):  
Susanne Nylén ◽  
Radheshyam Maurya ◽  
Liv Eidsmo ◽  
Krishna Das Manandhar ◽  
Shyam Sundar ◽  
...  

Visceral leishmaniasis (VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin (IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4+CD25+ (Foxp3high) regulatory T (T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3–4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon γ responses. In contrast, splenic T cells depleted of CD25+ cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10–producing CD25−Foxp3− T cells in the pathogenesis of human VL.


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