Il-12 and Neutralization of Endogenous Il-10 Revert the in Vitro Antigen-Specific Cellular Immunosuppression of Paracoccidioidomycosis Patients

Romano, Carla Cristina; Mendes-Giannini, María José Soares; Duarte, Alberto J. S.; Benard, Gil

doi:10.1006/cyto.2002.0884

Cited by 66 publications

(52 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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). IFN-␥-producing cells, ϳ37% of CD4 ϩ CD25 ϩ T cells, were present in PCM lesions.…”

Section: Discussionmentioning

confidence: 87%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 87%

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

View full text Add to dashboard Cite

show abstract

“…In this regard, we showed a few years ago that IL-10 has a major role in the down modulation of the Th-1 immune responses. Blockade of IL-10 could in vitro redress the gp43-induced IFN-c release of patients with severe, untreated disease [52]. INF-c is considered a critical cytokine in anti-Pb immunity, at least in experimental models of PCM [53].…”

Section: Modifying the Immune Responses?mentioning

confidence: 99%

An overview of the immunopathology of human paracoccidioidomycosis

2008

Self Cite

View full text Add to dashboard Cite

We review here the advances in the understanding of the immunopathology of human paracoccidioidomycosis (PCM). Its investigation must take in account the intriguing natural history of the mycosis and its agent, providing clues to the mechanisms that lead to development of disease (unbalanced host-parasite relationship?) or to the clinically silent, chronic carrier state (balanced hostparasite relationship?), in exposed people living in endemic areas. Although the literature on this subject has progressed notably, the overall picture of what are the mechanisms of susceptibility or resistance continues to be fragmentary. Major advances were seen in the description of both the cytokines/chemokines associated to the different outcomes of the hostparasite interaction, and the fungus-monocyte/macrophage interaction, and cytokines released thereof by these cells. However, relatively few studies have attempted to modify, even in vitro, the patients' unbalanced immune reactivity. Consequently, the benefits of this improved knowledge did not yet reach clinical practice. Fortunately, the previous notion of the immune system as having two nearly independent arms, the innate and adaptive immunities, leaving a large gap between them, is now being overcome.Immunologists are now trying to dissect the connections between these two arms. This will certainly lead to more productive results. Current investigations should address the innate immunity events that trigger the IL-12/IFN-c axis and confer protection against PCM in those individuals living in endemic areas, who have been infected, but did not develop the mycosis.

show abstract

“…P. brasiliensis induces an inflammatory response that leads to the formation of granulomas containing a compact collection of cells of the mononuclear phagocytic system, which is the location of the primary lesion in PCM in order to contain and destroy the fungi and prevent its spread. Macrophages and CD4 + T lymphocytes assume central importance in the morphogenesis of the inflammatory process and the synergistic action of these cells is important in the formation and modulation of the granulomas (Ruas et al, 2009;Sadahiro, Diogo, Oshiro, & Shikanai-Yasuda, 2007;Arruda et al, 2002;Romano, Mendes-Giannini, Duarte, & Benard, 2002;Fortes, Kurokawa, Marques, Miot, & Marques, 2011). The CD8 lymphocytes may play an important role in the pathogenesis of pulmonary PCM, because these cells were found in patients with PCM along with pro-inflammatory cytokines produced by alveolar macrophages and specific P. brasiliensis antibodies (Chiarella et al, 2007;Fornazim et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

<b>Influence of n-3 Polyunsaturated Fatty Acid in the Proliferative Activity of Lymphocytes During Experimental Infection with <i>Paracoccidioides brasiliensis

Navarini

Sargi²,

Visentainer

et al. 2018

Acta Sci. Health Sci.

View full text Add to dashboard Cite

ABSTRACT. It has been shown that diets containing polyunsaturated omega-3 fatty acids may modulate the immune system. Paracoccidioidomycosis (PCM) is a systemic mycosis of great importance in Latin America, caused by the thermo-dimorphic fungus Paracoccidioides brasiliensis. The aim of this study was to evaluate the influence of n-3 PUFAs in lymphoproliferative activity in murine experimental PCM. Spleen lymphocytes from animals infected with an isolate of P. brasiliensis (Pb18) and fed with diets supplemented with flaxseed oil or a commercial diet for eight weeks, were obtained and cultured for evaluation of lymphoproliferative activity by MTT assay. In uninfected animals and those fed an enriched-flaxseed diet the evaluated lymphoproliferative activity was inhibited in the first week; however, this activity resumed at later stages. On the other hand, in animals infected and fed an enriched-flaxseed diet, the interaction between the stimulus given by the presence of the fungus and the action of n-3 PUFAs appeared to stimulate lymphocyte proliferation after the first week of infection. n-3 PUFAs are shown to influence lymphoproliferative activity of mice in experimental PCM.Keywords: omega-3, paracoccidioidomycosis, imune cell.Influência do ácido graxo poli-insaturado n-3 na atividade proliferativa de linfócitos durante a infecção com Paracoccidioides brasiliensis RESUMO. Tem-se demonstrado que dietas contendo ácido graxo poli-insaturado ômega-3 podem modular o sistema imune. A Paracoccidioidomicose é uma micose sistêmica de grande importância na América Latina, causada pelo fungo termo-dimórfico Paracoccidioides brasiliensis. O objetivo do estudo foi avaliar a influência do AGPI n-3 na atividade linfoproliferativa na PCM experimental murina. Linfócitos esplênicos de animais infectados com o isolado de P. brasiliensis e alimentados com uma dieta suplementada com óleo de linhaça por 8 semanas, foram obtidos e cultivados para avaliação da atividade linfoproliferativa através do ensaio de MTT. Nos animais não infectados e alimentados com a dieta enriquecida com linhaça houve a inibição da atividade linfoproliferativa na primeira semana, sendo retomada no estágio mais tardio. Por outro lado, nos animais infectados e suplementados com a dieta com óleo de linhaça, a interação entre o estímulo dado pela presença do fungo e a ação do AGPI n-3 parecem ter estimulado a proliferação de linfócitos depois da primeira semana de infecção. AGPI n-3 podem ter influenciado a atividade linfoproliferativa dos camundongos na PCM experimental.Palavras-chave: ômega-3, paracoccidioidomicose, células imune.

show abstract

Il-12 and Neutralization of Endogenous Il-10 Revert the in Vitro Antigen-Specific Cellular Immunosuppression of Paracoccidioidomycosis Patients

Cited by 66 publications

References 36 publications

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

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

An overview of the immunopathology of human paracoccidioidomycosis

<b>Influence of n-3 Polyunsaturated Fatty Acid in the Proliferative Activity of Lymphocytes During Experimental Infection with <i>Paracoccidioides brasiliensis

Contact Info

Product

Resources

About