IMBALANCE OF IL-2, IFN-γ AND IL-10 SECRETION IN THE IMMUNOSUPPRESSION ASSOCIATED WITH HUMAN PARACOCCIDIOIDOMYCOSIS

Benard, Gil; Romano, Carla Cristina; Cacere, Camila R.; Juvenale, Michelangelo; Mendes-Giannini, María José Soares; Duarte, Alberto J. S.

doi:10.1006/cyto.2000.0824

Cited by 166 publications

(185 citation statements)

References 12 publications

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“…Some reports have suggested that monocytes from PCM patients are the main source of IL-10 (2,33). In this study we demonstrated that monocytes challenged with high virulence P. brasiliensis strain induce higher levels of inflammatory and anti-inflammatory cytokines compared to low virulence strain.…”

Section: Monocyte Cytokines Induced By Paracoccidioides Brasiliensissupporting

confidence: 58%

Pro‐ and Anti‐Inflammatory Cytokines Produced by Human Monocytes Challenged In Vitro with Paracoccidioides brasiliensis

Kurokawa

Araújo

Soares

et al. 2007

Microbiology and Immunology

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Monocytes and macrophages play a central role in innate and adaptive immune response against systemic fungal infections. Imbalances in suppressor or stimulatory cytokine secretion caused by these cells may influence disease development, microorganism death, and the nature of the adaptive immune response. This study analyzed the monocyte cytokine profiles of healthy individuals challenged with high and low virulent strains of P. brasiliensis and mRNA cytokine expression kinetics by reverse transcription polymerase chain reaction (RT‐PCR). Peripheral blood monocytes from healthy volunteers were cultured in vitro with and without virulent (Pb18) or low virulence (Pb265) strains from P. brasiliensis viable yeast cells. Interleukin‐1 beta (IL‐1β), IL‐6, IL‐8, IL‐10, tumor necrosis factor‐alpha (TNF‐α), and transforming growth factor‐beta (TGF‐β1) were measured in culture supernatants by enzyme immunoassay (ELISA), and mRNA cytokine expression was determined by RT‐PCR at 0, 4, 8, 12, 18 and 48 hr. Both P. brasiliensis strains induced monocyte production of IL‐1β, IL‐6, IL‐10 and TNF‐α. Pb18 induced higher levels of IL‐1β, IL‐6, and IL‐10 than Pb265. IL‐8 and TGF‐β1 levels were not significantly different from those cultured without stimulus. The mRNA cytokine expression was similar to supernatant cytokines measured by ELISA. In vitro monocyte challenge with virulent P. brasiliensis strain induces earlier and higher levels of pro‐ and anti‐inflammatory cytokines than low virulence strain.

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Section: Monocyte Cytokines Induced By Paracoccidioides Brasiliensissupporting

confidence: 58%

Pro‐ and Anti‐Inflammatory Cytokines Produced by Human Monocytes Challenged In Vitro with Paracoccidioides brasiliensis

Kurokawa

Araújo

Soares

et al. 2007

Microbiology and Immunology

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“…These data suggest that distinct subsets of CD4 ϩ T cells with regulatory properties are present in P. brasiliensis-induced lesions (i.e., IL-10-producer T cells, Tr1). Although we did not define the specificity of production IL-10 by CD4 ϩ CD25 ϩ T cells as well as their role in the Treg cell function, this immunoregulatory cytokine has been described to play an important role in impairment of the cell-mediated immune response of patients with PCM (9,12,13). Indeed, the addition of anti-IL-10 partially restored T cell proliferation and IFN-␥ production (43).…”

Section: Discussionmentioning

confidence: 87%

“…However, the patients with PCM usually show impaired cellular immune response to fungal Ags (3,7,8). Imbalance in cytokine production (9), with decreased IFN-␥ (10) and increased TGF-␤ (8,11) and IL-10 production (9,12,13), high levels of Fas-L and CTLA-4 expression in T cells (8), and apoptosis-induced cell death (8,14) are postulated to be involved in the T cell unresponsiveness seen in these patients. Interesting, impaired T cell proliferation, CTLA-4 expression, and TGF-␤ and IL-10 production are also involved in regulation of the effector immune response mediated by regulatory T (Treg) cells (15,16).…”

Section: O Ne Of the Most Important Endemic Diseases In Latinmentioning

confidence: 99%

Systemic and Local Characterization of Regulatory T Cells in a Chronic Fungal Infection in Humans

Cavassani¹,

Campanelli²,

Moreira³

et al. 2006

The Journal of Immunology

129

106

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The long-term persistence of pathogens in a host is a hallmark of certain infectious diseases, including schistosomiasis, leishmaniasis, and paracoccidioidomycosis (PCM). Natural regulatory T (Treg) cells are involved in control of the immune responses, including response to pathogens. Because CTLA-4 is constitutively expressed in Treg cells and it acts as a negative regulator of T cell activation in patients with PCM, here we investigated the involvement of Treg cells in the control of systemic and local immune response in patients with PCM. We found that the leukocyte subsets were similar in patients and controls, except for CD11c+CD1a+ cells. However, a higher frequency of CD4+CD25+ T cells expressing CTLA-4, glucorticoid-inducible TNFR, membrane-bound TGF-β, and forkhead-box 3 were observed in PBMC of patients. In accordance, these cells exhibited stronger suppressive activity when compared with those from controls (94.0 vs 67.5% of inhibition of allogeneic T cell proliferation). In addition, the data showed that CD4+CD25+ T cells expressing CTLA-4+, glucocorticoid-inducible TNFR positive, CD103+, CD45RO+, membrane-bound TGF-β, forkhead-box 3 positive, and the chemokines receptors CCR4 and CCR5 accumulate in the Paracoccidioides brasiliensis-induced lesions. Indeed, the secreted CCL17 and CCL22, both associated with the migration of Treg cells to peripheral tissues, were also detected in the biopsies. Moreover, the CD4+CD25+ T cell derived from lesions, most of them TGF-β+, also exhibited functional activity in vitro. Altogether, these data provide the first evidence that Treg cells play a role in controlling local and systemic immune response in patients with a fungal-induced granulomatous disease advancing our understanding about the immune regulation in human chronic diseases.

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“…Considering the suppressor effects of IL-10, its production in response to various microorganisms, including fungi, has been regarded as an important host evasion mechanism (Redpath et al 2001). The same mechanism could explain the activity of Pb18, as high concentrations of this cytokine were detected in patients' serum (Fornari et al 2001) and in peripheral blood cell culture supernatants (Benard et al 2001, Oliveira et al 2002. Moreover, monocytes from patients ) and monocytes from normal individuals challenged with the fungus (Kurokawa et al 2007) spontaneously release high concentrations of this cytokine in vitro.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis

Bannwart

Martins

Nakaira-Takahashi

et al. 2010

Mem. Inst. Oswaldo Cruz

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IMBALANCE OF IL-2, IFN-γ AND IL-10 SECRETION IN THE IMMUNOSUPPRESSION ASSOCIATED WITH HUMAN PARACOCCIDIOIDOMYCOSIS

Cited by 166 publications

References 12 publications

Pro‐ and Anti‐Inflammatory Cytokines Produced by Human Monocytes Challenged In Vitro with Paracoccidioides brasiliensis

Pro‐ and Anti‐Inflammatory Cytokines Produced by Human Monocytes Challenged In Vitro with Paracoccidioides brasiliensis

Systemic and Local Characterization of Regulatory T Cells in a Chronic Fungal Infection in Humans

Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis

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