Antigen-Specific Immunosuppression in Paracoccidioidomycosis

Benard, Gil; Ma, Hong; Negro, G. Del; Batista, Luis Francisco Zirnberger; Shikanai-Yasuda, Maria Aparecida; Aj, Duarte

doi:10.4269/ajtmh.1996.54.7

Cited by 71 publications

(56 citation statements)

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“…29 Another study on the in vitro response of lymphocytes from patients with paracoccidioidomycosis showed an inverse correlation of P. brasiliensis antigen response with eosinophil levels and anti-P. brasiliensis antibody levels. 30 A related disease, coccidioidomycosis, is endemic in the desert area of the southwestern United States. Previous studies show that coccidioidomycosis is frequently accompanied by an increase in peripheral blood eosinophils in the range of 3-10%.…”

Section: Discussionmentioning

confidence: 99%

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Wagner

Franco

Kephart

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Paracoccidioidomycosis is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Although eosinophils have long been associated with the immune defense against helminths, the role of eosinophils in the immune response to fungal diseases is not as well studied. The eosinophil granule major basic protein is toxic to helminths and mammalian cells in vitro, and its release has been used as a marker of eosinophil localization and degranulation. To determine whether eosinophil infiltration and degranulation, as evidenced by the deposition of major basic protein, occur in lesions of P. brasiliensis, we used an immunofluorescence technique to localize the P. brasiliensis organisms and eosinophils and major basic protein. Initially, all tissues were stained with polyclonal antibody to major basic protein; subsequently, colocalization of major basic protein and P. brasiliensis by double staining with mouse and rabbit antibodies, respectively, was performed. Nine biopsy tissues from seven patients were analyzed. All nine biopsies showed infiltration of intact eosinophils using both the monoclonal and the polyclonal anti-major basic protein antibodies, along with the presence of P. brasiliensis. Furthermore, using the polyclonal antimajor basic protein antibody, nine of nine tissues showed extracellular major basic protein deposition (granular or diffuse fluorescence staining outside of intact eosinophils). The double staining procedure using the anti-major basic protein monoclonal antibody showed extracellular deposition in five of eight biopsies; in these five biopsies, approximately 60% of the areas containing P. brasiliensis had extracellular major basic protein deposited on the organisms. These observations support the hypothesis that the eosinophil, through toxic granule proteins such as major basic protein, participates in the pathophysiology of paracoccidioidomycosis.

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Section: Discussionmentioning

confidence: 99%

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Wagner

Franco

Kephart

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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“…Accordingly, these patients are characterized by severe immunosuppression as evidenced by the failure to respond to P. brasiliensis antigens in terms of delayed-type hypersensitivity and lymphoproliferative response in vitro. 28,29 Baida and others 30 investigated the antibody response to the major P. brasiliensis antigen (gp-43-kDa) in juvenile and adult clinical forms of PCM. The IgG4 isotype was detected in all patients with the JF of PCM but only in 12% of the patients with the AF of PCM.…”

Section: Resultsmentioning

confidence: 99%

Capture enzyme-linked immunosorbent assay to detect specific immunoglobulin E in sera of patients with paracoccidioidomycosis.

Mamoni¹,

Rossi²,

Camargo³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Paracoccidioidomycosis (PCM) is the most frequent systemic mycosis in South America. The disease is characterized by a polyclonal activation of B cells, resulting in hyperimmunoglobulinemia. The production of immunoglobulin (Ig) E in deep mycosis has been related to the severity of the disease. However, the detection of specific IgE in sera of patients is difficult because of the competition with the IgG. We compared a capture and an indirect enzyme-linked immunosorbent assay (ELISA) technique to detect Paracoccidioides brasiliensis IgE. We found that the capture ELISA presented higher performance and lower background values than the indirect assay, resulting in a significant quantitative discrimination between sera from patients with the 2 major clinical forms of PCM. Patients with the juvenile form presented significantly higher levels of P. brasiliensis IgE, as compared with patients with the adult form. The capture ELISA was used in the follow-up of patients receiving treatment, showing that the levels of specific IgE decreased as the patient's clinical conditions improved.

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“…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.…”

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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Antigen-Specific Immunosuppression in Paracoccidioidomycosis

Cited by 71 publications

References 0 publications

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

Capture enzyme-linked immunosorbent assay to detect specific immunoglobulin E in sera of patients with paracoccidioidomycosis.

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

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