Effect of cytokines on the in vitro fungicidal activity of monocytes from paracoccidioidomycosis patients

Calvi, Sueli Aparecida; Peraçoli, Maria Terezinha Serrão; Mendes, Rinaldo Pôncio; Marcondes-Machado, Jussara; Fecchio, Denise; Marques, Sílvio Alencar; Soares, Ana Flávia

doi:10.1016/s1286-4579(02)00078-3

Cited by 77 publications

(86 citation statements)

References 21 publications

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“…Several groups addressed this question by quantifying the cytokines released in vitro from patients' cells. The results published so far were, in general, quite concordant and the picture that emerged were quite consistent, as depicted in Table 2 [19,25,[27][28][29][30][31][32][33][34]. In brief, these studies showed that the acute/subacute form of the disease is associated with down modulation of the Th-1 cytokine pattern and expression of a dominant Th-2 immunity consisting of high levels of a subset of cytokines such as IL-4, IL-5 and IL-10, specific antibodies of the IgE and IgG4 subclasses, in situ and peripheral blood eosinophilia, among other parameters.…”

supporting

confidence: 64%

“…Thus IL-10 seems to be the major dominant negative cytokine in PCM patients, blocking the full expression of immunity mediated by the IFN-c/IL-12 axis and the fungicidal activity of macrophages. Other studies have shown that TNF-a was the most potent agonist of Pb fungicidal activity by macrophages from both healthy donors and patients, provided the cells have been pre-activated with IFN-c [31]. GM-CSF as well was able to increase the fungicidal activity of human macrophages [57], while prostaglandins were shown to strongly inhibit it [46].…”

Section: Modifying the Immune Responses?mentioning

confidence: 99%

“…The cytokine balance certainly plays a role in this ''decision'': adequate macrophage activation would be needed to increase its anti-fungal properties as suggested by the observation that macrophages from healthy donors exhibit very limited in vitro activity against virulent Pb strains (£5% reduction in the number of CFU), as compared to less virulent strains [31,46]. In fact, macrophages isolated from patients' peripheral blood exhibited slightly higher, but still weak in vitro killing capacity against virulent Pb (only *10-15% reduction in the number of CFU) [31,46]. This slight enhancement was accounted for the more activated status of patients' cells due to their previous, in vivo, exposure to fungal antigens.…”

mentioning

confidence: 99%

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An overview of the immunopathology of human paracoccidioidomycosis

2008

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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.

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supporting

confidence: 64%

Section: Modifying the Immune Responses?mentioning

confidence: 99%

mentioning

confidence: 99%

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An overview of the immunopathology of human paracoccidioidomycosis

2008

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“…Previous studies on the fungicidal activity of human monocytes against Pb18 indicated that IFN-γ plays an important role in monocyte and macrophage activation, which leads to the inhibition of fungal replication in these cells (Calvi et al 2003). The synergistic effects of IFN-γ and GM-CSF on MGC formation were also observed in the fungicidal activity of these cells against Pb18.…”

Section: Discussionmentioning

confidence: 87%

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Bannwart

Nakaira-Takahagi

Peraçoli

2011

Mem. Inst. Oswaldo Cruz

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Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18). The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18

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“…The mechanism of b-glucan host protection may be related to its capacity to stimulate inflammatory mediators such as tumor necrosis factor-alpha (TNF-a). Since TNF-a has been associated with resistance to P. brasiliensis [46,47], fks down-regulation may be an important adaptive mechanism of P. brasiliensis to reduce the inflammatory response elicited by the host [30]. In addition, transcripts related to remodelling cell wall and osmotic stress (gln1, glutamine synthetase; septin-1, sho1, pas-like) were also induced in P. brasiliensis upon blood contact [31].…”

Section: Transcriptional Profile Of P Brasiliensis Upon Infectionmentioning

confidence: 99%

Insights into the pathobiology of Paracoccidioides brasiliensis from transcriptome analysis—advances and perspectives

et al. 2008

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Paracoccidioiddes brasiliensis is a thermodimorphic fungus endemic to Latin America, where it causes the most prevalent systemic mycosis, paracoccidioidomycosis (PCM). DNA microarray technology has been used to identify patterns of gene expression when a microbe is confronted with conditions of interest, such as in vitro and/or ex vivo interaction with specific cells. P. brasiliensis is one organism that has benefited from this approach. Even though its genome has not been sequenced yet, much has been discovered from its transcriptome and DNA array analyses. In this review, we will outline the current knowledge in P. brasiliensis transcriptome, with focus on differential expression analysis in vitro and on the discussion of the genes that are controlled during the host-pathogen interaction ex vivo in order to give insights into the pathobiology of this fungus. In vitro experiments enabled the delineation of whole metabolic pathways; the description of differential metabolism between mycelium and yeast cells and of the mainly signaling pathways controlling dimorphism, high temperature growth, thermal and oxidative stress, and virulence/ pathogenicity. Recent ex vivo experiments provided advances on the comprehension of the plasticity of response and indicate that P. brasiliensis is not only able to undergo fast and dramatic expression profile changes but can also discern subtle differences, such as whether it is being attacked by a macrophage or submitted to the bloodstream route conditions.

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Effect of cytokines on the in vitro fungicidal activity of monocytes from paracoccidioidomycosis patients

Cited by 77 publications

References 21 publications

An overview of the immunopathology of human paracoccidioidomycosis

An overview of the immunopathology of human paracoccidioidomycosis

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Insights into the pathobiology of Paracoccidioides brasiliensis from transcriptome analysis—advances and perspectives

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