Interleukin-10 and the pathogenesis of human visceral leishmaniasis

Nylén, Susanne; Sacks, David L.

doi:10.1016/j.it.2007.07.004

Cited by 338 publications

(334 citation statements)

References 92 publications

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“…On the other hand, spleen cells obtained from infected malnourished mice were not able to produce IFN-γ when stimulated with L. chagasi antigen. Since IL-10 is a cytokine with many suppressive effects (Nylén & Sacks 2007), we analyzed the production of this cytokine by spleen cells obtained from the different experimental groups. No differences were observed in the levels of IL-10 between mice fed the control or malnutrition diets or between infected and uninfected mice, indicating that VL in mice is not characterized by high levels of IL-10.…”

Section: Resultsmentioning

confidence: 99%

“…In fact, in BALB/c mice, the control of visceral infection is associated with the development of parasitespecific cell-mediated immune responses involving both CD4 + and CD8 + T cells (Carrión et al 2006). Although IL-10 is a cytokine with suppressive effects (Mansueto et al 2007, Nylén & Sacks 2007, no difference was detected in its level between control and malnutrition groups. No production of IL-4 and NO by spleen cells was detected in the experimental groups through the methods used.…”

Section: Discussionmentioning

confidence: 99%

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Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Serafim¹,

Malafaia

Silva³

et al. 2010

Mem. Inst. Oswaldo Cruz

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Serafim¹,

Malafaia

Silva³

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…Finally, it is already known that human VL is associated with high levels of IL-10. As such, suppression of this cytokine might be important for disease because it is involved in the suppression of macrophage activity (Nylén & Sacks 2007).…”

Section: Discussionmentioning

confidence: 99%

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

Grenfell

Silva

Testasicca

et al. 2010

Mem. Inst. Oswaldo Cruz

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This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasiinfection. These immunogenic preparations were composed of Leishmania amazonensisor Leishmania braziliensisantigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasiby intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensisantigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasiantigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication

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“…It has also been found to be important in susceptibility to visceral leishmaniasis 30,49 . It has been detected in different samples of human visceral leishmaniasis: as mRNA in bone marrow 36 , lymph node 27 , and spleen 38 aspirates and at high levels in serum 1,2,15,40,50,52,63,69 ; for further information see 51 . As mentioned earlier, the possible effect of IL-10 on the production of, or proliferation of IFN-g producing cells 11,28 may not be important given the high activation of the immune response in lymphoid organs during active disease.…”

Section: Immunoactivation In Lymphoid Organsmentioning

confidence: 99%

Immunoactivation and immunopathogeny during active visceral leishmaniasis

Goto

Prianti

2009

Rev. Inst. Med. trop. S. Paulo

101

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SUMMARYVisceral leishmaniasis is caused by protozoan parasites of the Leishmania donovani complex. During active disease in humans, high levels of IFN-g and TNF-a detected in blood serum, and high expression of IFN-g mRNA in samples of the lymphoid organs suggest that the immune system is highly activated. However, studies using peripheral blood mononuclear cells have found immunosuppression specific to Leishmania antigens; this poor immune response probably results from Leishmania antigen-engaged lymphocytes being trapped in the lymphoid organs. To allow the parasites to multiply, deactivating cytokines IL-10 and TGF-b may be acting on macrophages as well as anti-Leishmania antibodies that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver and can be confirmed through the examination of organ samples. However, an analysis of sequential data from studies of visceral leishmaniasis in hamsters suggests that factors outside of the immune system are responsible for the early inactivation of inducible nitric oxide synthase, which occurs before the expression of deactivating cytokines. In active visceral leishmaniasis, the immune system actively participates in non-lymphoid organ lesioning. While current views only consider immunocomplex deposition, macrophages, T cells, cytokines, and immunoglobulins by diverse mechanism also play important roles in the pathogenesis. KEYWORDS:Visceral leishmaniasis; Human; Immunosuppression; Immunoactivation; Cytokines; Immunopathogenesis.Visceral leishmaniasis is caused by protozoa of the genus Leishmania that are transmitted to mammalian hosts, including humans, by phlebotomine sandflies. The disease is present in 66 countries in tropical and subtropical regions, and 90% of cases occur in India, Sudan, Bangladesh, Nepal, and Brazil. It is estimated that there are 500,000 new cases a year worldwide 68 , and 3,000 new cases occur each year in Brazil 48 . Until recently, the disease was thought to be caused by three species of the Leishmania donovani complex: Leishmania (Leishmania) donovani, L. (L.) infantum, and Leishmania (L.) chagasi (a species present in Brazil). There is now debate, however, over whether L. (L). infantum and Leishmania (L.) chagasi are the same 44 or different 60 species. In this review, the names of the three species will be used as in the original publications. Leishmania (Leishmania) donovani is present in East Africa, India, and parts of the Middle East, while L. (L.) infantum in Europe, North Africa, and South and Central America. Human infections can be asymptomatic or can manifest as oligosymptomatic and progressive diseases; progressive cases can involve hepatosplenomegaly, fever, pancytopenia, hypergammaglobulinemia, and serious weight loss 4 . During active visceral leishmaniasis, the parasite multiplies within the cells of the mononuclear phagocyte system in the spleen, liver, and bone marrow, and the disease is fatal if untreated.Studies...

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Interleukin-10 and the pathogenesis of human visceral leishmaniasis

Cited by 338 publications

References 92 publications

Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

Immunoactivation and immunopathogeny during active visceral leishmaniasis

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