Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of Human<i>Leishmania (L.) infantum chagasi</i>Infection

Ramos, Patrícia Karla Santos; Carvalho, Karina I.; Rosa, Daniela Santoro; Rodrigues, Ana Paula; Lima, Luciana Campos; Campos, Marliane Batista; Gomes, C. M. C.; Laurenti, Márcia Dalastra; Corbett, Carlos Eduardo Pereira; Sílveira, Fernando Tobias

doi:10.1155/2016/6937980

Cited by 19 publications

(19 citation statements)

References 28 publications

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“…In agreement with our results around the levels of IFN‐γ, it has been reported that in human VL, the response is predominantly Th2‐type with absence of PBMCs derived IFN‐γ 37 . However, other studies reported significant up‐regulation of IFN‐γ, TNF‐α, 38,39 IL‐1β 40 and IL‐33 41 in the sera of the patients with active VL. This discrepancy may be due to the differences in the age, ethnic and racial diversity and the species of Lesihmania as well as the sample size.…”

Section: Discussionmentioning

confidence: 81%

“…In agreement with our results around the levels of IFN-γ, it has been reported that in human VL, the response is predominantly Th2-type with absence of PBMCs derived IFN-γ. 37 However, other studies reported significant up-regulation of IFN-γ, TNF-α, 38,39 IL-1β 40 and IL-33 41 To Our study has some limitations such as lower sample size, lack of determining parasite burden during treatment and long-term follow-up to determine VL recurrence.…”

Section: F I G U R Ementioning

confidence: 84%

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Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Moravej

Choopanizadeh

Pourabbas

et al. 2020

Parasite Immunology

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IL-9 + CD4+T cells comprise a heterogeneous population of T cells including T helper (Th)-2, 1 Th17, 2 regulatory T cells 3 and a recently discovered T-cell subset named Th9. 4 Closely related to Th2, Th9 is deviated from naïve CD4+ T cells in the presence of transforming growth factor (TGF)-β, interleukin (IL)-4, IL-21, tumour necrosis factor (TNF)-α and IL-10. 5-8 Although IL-9 is known as prototype cytokine of Th9, these cells cannot produce other cytokines such as IL-4, IL-5, IL-13 and interferon (IFN)-γ. 9 To produce IL-9, several cytokines (IL-1α/β, IL-2, IFN-α and IL-33) are considered as the activators, 5 and on the other hand, interferon (IFN)-γ is reported to play inhibitory effects on Th9 differentiation and IL-9 production both in vitro and in vivo. 10 Collectively, as shown in Figure 1, various cytokines are involved in the differentiation of IL-9 + CD4+T cells as well as IL-9 secretion. Although the role of IL-9 + CD4+T cells and its prominent cytokine, IL-9, has been clarified in the autoimmune diseases, 11 allergic diseases 12,13 and tumours, 14 limited studies have investigated its role in the infectious diseases. Leishmaniasis, as an infectious disease, is caused by obligatory intracellular protozoan parasite belonging to the genus Leishmania (L). Based on the Leishmania species, host genetics, interaction between host immune system and parasites and the load of Leishmania entrance, the clinical manifestations of the disease range from self-healing cutaneous leishmaniasis (CL) to life-threatening form of visceral leishmanisis (VL)

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Section: Discussionmentioning

confidence: 81%

Section: F I G U R Ementioning

confidence: 84%

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Moravej

Choopanizadeh

Pourabbas

et al. 2020

Parasite Immunology

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“…In contrast, IL-6 deficient C57BL/6 mice were able to control the infection by L. major as the wild type corresponding mice (Moskowitz et al, 1997). Furthermore, multiple studies have shown a correlation between the high level of some cytokines, including IL-6, and the severity of visceral leishmaniasis (Ansari et al, 2006; Van Den Bogaart et al, 2014; Dos Santos et al, 2016; Ramos et al, 2016) and cutaneous leishmaniasis (Latifynia et al, 2012; Espir et al, 2014). To our knowledge, this is the first study addressing the determination of IL-6 protein levels produced by human neutrophils after exposure to Leishmania species.…”

Section: Discussionmentioning

confidence: 99%

Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Oualha

Barhoumi

Marzouki

et al. 2019

Front. Cell. Infect. Microbiol.

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Leishmaniases are neglected diseases, caused by intracellular protozoan parasites of the Leishmania ( L .) genus. Although the principal host cells of the parasites are macrophages, neutrophils are the first cells rapidly recruited to the site of parasites inoculation, where they play an important role in the early recognition and elimination of the parasites. The nature of early interactions between neutrophils and Leishmania could influence the outcome of infection. Herein we aimed to evaluate whether different Leishmania strains, responsible for distinct clinical manifestations, could influence ex vivo functional activity of neutrophils. Human polymorphonuclear leukocytes were isolated from 14 healthy volunteers and the ex vivo infection of these cells was done with two L. infantum and one L. major strains. Infection parameters were determined and neutrophils activation was assessed by oxidative burst, degranulation, DNA release and apoptosis; cytokine production was measured by a multiplex flow cytometry analysis. Intracellular amastigotes were rescued to determine Leishmania strains survival. The results showed that L. infantum and L. major promastigotes similarly infected the neutrophils. Oxidative burst, neutrophil elastase, myeloperoxidase activity and apoptosis were significantly increased in infected neutrophils but with no differences between strains. The L. infantum -infected neutrophils induced more DNA release than those infected by L. major . Furthermore, Leishmania strains induced high amounts of IL-8 and stimulated the production of IL-1β, TNF-α, and TGF-β by human neutrophils. We observed that only one strain promoted IL-6 release by these neutrophils. The production of TNF-α was also differently induced by the parasites strains. All these results demonstrate that L. infantum and L. major strains were able to induce globally a similar ex vivo activation and apoptosis of neutrophils; however, they differentially triggered cytokines release from these cells. In addition, rescue of intracellular parasites indicated different survival rates further emphasizing on the influence of parasite strains within a species on the fate of infection.

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“…Because IL-4 plays a crucial role in VL susceptibility and progression [30] and is involved in the regulation of IFN-γ production, its absence has a positive effect on the progression from subclinical disease to spontaneously resolved infection [8]. In our study period, IL-4 levels increased in previously infected individuals.…”

Section: Plos Onementioning

confidence: 72%

“…The mechanisms by which asymptomatic individuals can contain parasite multiplication and control infection remain unknown [3,8]. In terms of parasite control, only the joint effect of cytokines, but not their isolated effects, could be evaluated in the present study, but the results suggest that infection control may involve a balance between IL-17 and IL-10.…”

Section: Discussionmentioning

confidence: 92%

Cytokine profile in Leishmania-positive blood donors

et al. 2020

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Serum levels of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17 (IL-17), interferon gamma (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β), cytokines involved in the immune response, were investigated in 75 Leishmania-positive blood donors living in endemic areas. Based on their status in 2011 and 2015, the subjects were clustered into three groups: positive for at least one diagnostic method in both years, but lacking clinical progression to disease (G1); positive on at least one method in 2011 but negative in 2015 (G2); negative on all methods in both years (G3). Donors were interviewed for sociodemographic data collection and underwent clinical evaluation and laboratory tests. Serum cytokines were quantified using a CBA Flex set (BD Biosciences). Significant differences were found for all the cytokines evaluated, with lower concentrations in consistently Leishmania-negative individuals. The exception was IFN-γ, with similar levels among all donors. No changes consistent with active disease were observed in the laboratory results for Leishmania-positive donors who underwent clinical evaluation, none of whom progressed to disease. This suggests that infection control is associated with serum IL-17 levels. Resolution of Leishmania infection in positive donors may be related to high levels of IL-17 and low levels of IL-10, highlighting the role played by IL-17 in asymptomatic Leishmania-infected individuals.

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Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of HumanLeishmania (L.) infantum chagasiInfection

Cited by 19 publications

References 28 publications

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Cytokine profile in Leishmania-positive blood donors

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