Leishmania (Viannia) braziliensis amastigotes induces the expression of TNFα and IL-10 by human peripheral blood mononuclear cells in vitro in a TLR4-dependent manner

Júnior, Hélio Galdino; Gomes, Rodrigo Saar; Santos, Jéssica Cristina dos; Pessoni, Lívia Lara; Maldaner, Anetícia Eduarda; Marques, Stefanne M.; Gomes, Clayson Moura; Dorta, Miriam Leandro; Oliveira, Milton Adriano Pelli de; Joosten, Leo A. B.; Ribeiro‐Dias, Fátima

doi:10.1016/j.cyto.2016.09.009

Cited by 24 publications

(25 citation statements)

References 66 publications

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“…Of high interest, using a genomics approach and functional validation, we could show that NOD2, TLR4 and Dectin-1 receptors are involved in Leishmania-induced IL-32γ expression. Several C-type lectins, such as MR and Mincle have been described as recognition receptors for Leishmania [49][50][51] [12,52]. It is unlikely that MR is involved in the induction of IL-32γ since there were no SNPs identified that modulated the IL-32γ expression (S1B Fig).…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis

Santos¹,

Quixabeira²,

Silva³

et al. 2020

PLoS Negl Trop Dis

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Interleukin-32 is a novel inflammatory mediator that has been described to be important in the immunopathogenesis and control of infections caused by Leishmania parasites. By performing experiments with primary human cells in vitro, we demonstrate that the expression of IL-32 isoforms is dependent on the time exposed to L. amazonensis and L. braziliensis antigens. Moreover, for the first time we show the functional consequences of three different genetic variations in the IL32 (rs4786370, rs4349147, rs1555001) modulating IL-32γ expression, influencing innate and adaptive cytokine production after Leishmania exposure. Using a Brazilian cohort of 107 American Tegumentary Leishmaniasis patients and a control cohort of 245 healthy individuals, the IL32 rs4786370 genetic variant was associated with protection against ATL, whereas the IL32 rs4349147 was associated with susceptibility to the development of localized cutaneous and mucosal leishmaniasis. These novel insights may help improve therapeutic strategies and lead to benefits for patients suffering from Leishmania infections.

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Section: Discussionmentioning

confidence: 99%

Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis

Santos¹,

Quixabeira²,

Silva³

et al. 2020

PLoS Negl Trop Dis

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“…Few studies have evaluated monocytes activated by New World Leishmania infection/antigen. We showed that human monocytes can be activated by Leishmania braziliensis through toll ‐like receptor (TLR)4 to produce cytokines . In addition, parasites can induce TLR2 and TLR9 in human monocytes, increasing cytokine production .…”

Section: Introductionmentioning

confidence: 99%

“…We showed that human monocytes can be activated by Leishmania braziliensis through toll-like receptor (TLR)4 to produce cytokines. 7 In addition, parasites can induce TLR2 and TLR9 in human monocytes, increasing cytokine production. 8 In patients infected with L braziliensis, TLR9 expression could be associated with immunopathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

Alterations in monocyte subsets and cytokine production after TLR activation in American Cutaneous Leishmaniasis

Quixabeira

Pereira

Veras³

et al. 2019

Parasite Immunology

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Phenotypic and functional aspects of monocytes from Localized Cutaneous Leishmaniasis (LCL) patients were evaluated. The frequencies of monocyte subsets and TLR2/TLR4 expression were evaluated in fresh peripheral blood whereas cytokine production was evaluated in whole blood cell cultures stimulated with TLR agonists or Leishmania braziliensis antigen (Ag). CD16+ monocytes frequency was increased in patients compared with controls. A TLR4 agonist (LPS) induced expression of TNF and IL‐10 in monocyte subsets of patients and controls. The CD14+CD16+ monocytes expressed higher levels of these cytokines than CD14+CD16− cells. The levels of secreted TNF were higher in whole blood cell cultures from patients than controls after LPS/TLR4 or Ag stimulation. Whereas in controls there was a positive correlation between TNF and IL‐10 levels, this was not observed in stimulated cell cultures from patients. The high levels of LPS‐induced TNF were associated with the number of lesions and the percentages of CD14hiCD16+ monocytes. The levels of TLR2‐induced TNF were also associated with number of lesions. All monocyte subsets from patients expressed higher levels of TLR2 and TLR4 than controls. Data suggest that systemically activated monocytes contribute for an imbalance in pro‐ and anti‐inflammatory cytokine production during LCL, participating in the immunopathogenesis of the disease.

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“…Peripheral blood mononuclear cells (PBMCs) were isolated from patients and controls as described by Galdino et al [24] and were not ex vivo stimulated. The mRNA was isolated by the TRIzol (Invitrogen, Carlsbad, CA, USA) method, and quantitative polymerase chain reaction (qPCR) was performed as described by Dos Santos et al [25].…”

Section: Methodsmentioning

confidence: 99%

“…The concentrations of the cytokines IL-10 and TNF-α in the culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA) as previously described [24]. …”

Section: Methodsmentioning

confidence: 99%

Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients

Oliveira

Gomes

Gomides

et al. 2019

Neuroimmunomodulation

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Objective: Multiple sclerosis (MS) is a multifactorial chronic disease that affects the central nervous system (CNS). Toll-like receptors (TLRs) play a central role in cytokine production after pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and contribute to CNS damage in MS patients. Here, we evaluated the effects of interferon (IFN)-β treatment in TLR2 and TLR4-dependent cytokine production and mRNA expression in whole-blood cell cultures from MS patients. Methods: We evaluated cytokine production by ELISA from whole-blood cell culture supernatants and mRNA expression by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Results: In patients treated with IFN-β, tumor necrosis factor (TNF)-α production after exposure to TLR2 agonist (Pam₃Cys) was lower than in healthy controls and untreated MS patients. However, IFN-β treatment had no significant effect on TNF-α production after TLR4 agonist (LPS) stimulation. On the other hand, interleukin (IL)-10 production was increased in TLR4- but not in TLR2-stimulated whole-blood cell culture from MS patients under IFN-β treatment when compared to the controls. No differences in TNF-α or IL-10 mRNA expression in PBMCs from healthy controls and untreated or treated MS patients were detected, although PBMCs from treated patients presented higher levels of IL-32γ mRNA than those from controls. Conclusions: Our data suggest that IFN-β treatment alters the TLR-dependent immune response of PBMCs from MS patients. This may contribute to the beneficial effects of IFN-β treatment.

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Leishmania (Viannia) braziliensis amastigotes induces the expression of TNFα and IL-10 by human peripheral blood mononuclear cells in vitro in a TLR4-dependent manner

Cited by 24 publications

References 66 publications

Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis

Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis

Alterations in monocyte subsets and cytokine production after TLR activation in American Cutaneous Leishmaniasis

Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients

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