T cell subset and cytokine profiles in human visceral leishmaniasis during active and asymptomatic or sub-clinical infection with Leishmania donovani

Hailu, Asrat; Baarle, Debbie van; Knol, Gerlinde J.; Berhe, Nega; Miedema, Frank; Kager, Piet A.

doi:10.1016/j.clim.2005.06.015

Cited by 71 publications

(71 citation statements)

References 44 publications

(38 reference statements)

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“…IL-12 also plays a key role in the initiation and maintenance of Th1 responses and the subsequent production of IFN-γ (Ghalib et al 1995). However, studies using the sera of patients with VL from Iran (Khoshdel et al 2009), southeast Ethiopia (Hailu et al 2005) and Brazil (Caldas et al 2005) have shown significantly higher levels of IL-12 in patients with the active disease relative to those in asymptomatic and healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

Costa

Aquino

et al. 2012

Mem. Inst. Oswaldo Cruz

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It is not well established whether cytokine production differs in response to different clinical forms of visceral leishmaniasis (VL). In this work, we performed a cross-sectional study to investigate the plasma levels of cytokines [interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10 and IL-12] involved in the pathogenesis of VL in 80 subjects from VL endemic areas, including subjects with active VL, subjects with asymptomatic infection, subjects with cured VL and uninfected controls. The patients were recruited by sampling from a referral hospital and by random selection from a population-based cohort study. The results showed significant differences in the plasma concentration of all cytokines between the groups (p < 0.05). Patients with the active disease had higher plasma levels of IL-10, IL-4, INF-γ and TNF-α relative to the other groups and they produced more IL-12 than asymptomatic and cured subjects. Only the IL-2 concentration was higher in the asymptomatic and cured subjects relative to the patients with active disease (p < 0.05). Our results suggest that these cytokines can be used as markers in epidemiological studies conducted in endemic areas to distinguish between different clinical forms of VL. However, their usefulness should be confirmed in investigations conducted in other endemic areas

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Section: Discussionmentioning

confidence: 99%

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

Costa

Aquino

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…Although some studies evaluating cytokines in serum samples have either not detected or found low concentrations of 69,70 , other studies have produced conflicting results. IFN-g was detected in 17 of 44 patients in Iran 2 and in 13 of 15 patients in Brazil 20 ; in addition, high levels have been confirmed in patients in Asia, Europe, Africa, and Brazil 9,15,31,32,50,52 . These differing results are most likely not related to the selected patient groups or to the Leishmania species involved, but rather to the samples that were analyzed.…”

mentioning

confidence: 87%

“…Therefore, PBMCs would consist of a non-Leishmania antigen-specific population, which would fail to proliferate or produce cytokines upon Leishmania antigen stimulation. It is also possible that the PBMCs are pre-activated and cannot be further stimulated; this is less likely, however, since a study in Ethiopia compared individuals with active disease, cured disease, subclinical manifestations, asymptomatic disease, and no disease and found that memory (CD45RO + CD27 + ) CD4 + cells and naïve (CD45RO -CD27 + ) CD8 + cells were at their lowest levels in patients with the active disease 31 . Furthermore, the same study found that phorphol miristate acetate-and ionomycin-induced CD4 + and CD8 + cell IFN-g production was at its lowest level in patients with the active disease 31 .…”

Section: Immunoactivation In Lymphoid Organsmentioning

confidence: 99%

Immunoactivation and immunopathogeny during active visceral leishmaniasis

Goto

Prianti

2009

Rev. Inst. Med. trop. S. Paulo

100

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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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“…is critically mediated by gamma interferon (IFN-␥)-producing Th1 cells, which activate macrophages to produce leishmanicidal compounds, such as nitric oxide (NO) (2). Together with IFN-␥, the inflammatory cytokine interleukin-17A (IL-17A) also mediates protection against L. infantum (3,4). On the other hand, Th2 cytokines are involved in susceptibility to leishmaniasis (2,5).…”

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confidence: 99%

Interleukin-27 (IL-27) Mediates Susceptibility to Visceral Leishmaniasis by Suppressing the IL-17–Neutrophil Response

et al. 2016

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bThe relationship established between Leishmania infantum and the vertebrate host can lead to a self-healing infection or to the manifestation of visceral leishmaniasis, a chronic systemic infection associated with high rates of mortality. We hypothesized that regulatory cytokines, such as interleukin-27 (IL-27), play a role in susceptibility to L. infantum infection. IL-27 is a heterodimeric cytokine composed of IL-27p28 and EBi3 subunits which, when combined, bind to IL-27R, leading to STAT-1 and -3 activation, playing a role in the regulation of the immune response. We observed in this work that IL-27 regulates the Th1/Th17 profiles in a mouse model of visceral leishmaniasis (VL) caused by L. infantum. We showed here that the pathogen recognition by endosomal Toll-like receptors triggers a type I interferon (IFN) response, which acts through the type I IFN receptor and interferon regulatory factor 1 to induce IL-27 production by macrophages. Furthermore, IL-27 plays a major regulatory role in vivo, because Ebi3 ؊/؊ mice can efficiently control parasite replication despite reduced levels of IFN-␥ compared to wild-type mice. On the other hand, the absence of Ebi3 leads to exacerbated IL-17A production in the infected organs as well as in a coculture system, suggesting a direct regulatory action of IL-27 during L. infantum infection. As a consequence of exacerbated IL-17A in Ebi3 ؊/؊ mice, a greater neutrophil influx was observed in the target organs, playing a role in parasite control. Thus, this work unveiled the molecular steps of IL-27 production after L. infantum infection and demonstrated its regulatory role in the IL-17A-neutrophil axis. Visceral leishmaniasis (VL), or kala-azar, is a systemic chronic disease with high mortality rates if not treated. It is caused by the parasites Leishmania infantum and L. donovani, and it is estimated that 300,000 new cases and 20,000 deaths occur annually (http://www.who.int/mediacentre/factsheets/fs375/en/). After dermal inoculation by the sandfly vector, the parasite disseminates to the liver, spleen, bone marrow, and lymph nodes of susceptible hosts, causing symptoms such as hepatosplenomegaly, lymphadenopathy, anemia, constant fever, and immunosuppression (1). Even though it is considered one of the six most important parasitic diseases affecting humans, the immunobiology of VL is not completely understood and novel therapeutic approaches are desired.The immune response against Leishmania spp. is critically mediated by gamma interferon (IFN-␥)-producing Th1 cells, which activate macrophages to produce leishmanicidal compounds, such as nitric oxide (NO) (2). Together with IFN-␥, the inflammatory cytokine interleukin-17A (IL-17A) also mediates protection against L. infantum (3, 4). On the other hand, Th2 cytokines are involved in susceptibility to leishmaniasis (2, 5). Moreover, the regulatory cytokines IL-10, IL-21, and IL-27 are produced in the bone marrow of VL patients, suggesting their association with the disease (6).The cytokine IL-27 is a dimer composed of p28...

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T cell subset and cytokine profiles in human visceral leishmaniasis during active and asymptomatic or sub-clinical infection with Leishmania donovani

Cited by 71 publications

References 44 publications

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

Immunoactivation and immunopathogeny during active visceral leishmaniasis

Interleukin-27 (IL-27) Mediates Susceptibility to Visceral Leishmaniasis by Suppressing the IL-17–Neutrophil Response

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