Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/s12879-014-0552-x http://hdl.handle.net/11449/117331 |
Resumo: | Background: Paracoccidioidomycosis (PCM) is systemic mycosis caused by the thermal dimorphic fungus of genus Paracoccidioides, leading to either acute/subacute (AF) or chronic (CF) clinical forms. Numerous CF patients after treatment exhibit sequels, such as pulmonary and adrenal fibrosis. Monocytes are cells that are involved in the inflammatory response during active infection as well as in the fibrogenesis. These cells comprise a heterogeneous population with distinct phenotypic and functional activities. The scope of this study was to identify changes regarding functional and phenotypical aspects in monocytes comparing CF PCM patients on antifungal treatment versus non-treated patients (PMC-p).Methods: Twenty-three CF PCM composed of 11 non-treated patients (NTG) and 12 patients in apparent cure (ACG) were studied. Sixteen healthy individuals were used as control group (CG). Monocyte subsets were determined by immunophenotyping based on CD14 and CD16 expression. Cellular function was measured in vitro with and without stimulation with lipopolysaccharide (LPS) and P. brasiliensis exoantigen (PbAg) for 24 hours. Independent samples were compared using unpaired t tests, dependent samples were analyzed by paired t-test. Groups of more than two independent samples were analyzed using an ANOVA, with Tukey's post-test. Significance was set up at p < 0.05.Results: Our results showed high counts of peripheral blood CD14(+)CD16(+) and CD14(+)CD16(++) monocytes in untreated PCM-p accompanied by intense production of pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and profibrotic growth factors (TGF-beta 1 and bFGF) by monocytes challenged with P. brasiliensis antigens. After the introduction of antifungal therapy, the counts of CD14(+)CD16(+) cells returned to baseline while CD14(+)CD16(++) counts remained high. Interestingly, counts of CD14(+)CD16(++) monocytes remained elevated even 52 +/- 7 months after successful antifungal treatment. Furthermore, the ACG-patients showed preserved pro-inflammatory activity in the presence of specific antigen stimuli and high spontaneous production of TNF-a by monocytes.Conclusions: Infection with Paracoccidioides leads to initiation of a specific proinflammatory response by monocytes of PCM-p during active disease and in the apparent cure. A profibrotic profile by monocytes was observed only at admission. Furthermore, PCM-p with apparent cure showed high spontaneous production of TNF-alpha and high counts of CD14(+)CD16(++) monocytes, probably induced by hypoxia duo to fibrotic sequelae. |
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Repositório Institucional da UNESP |
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2946 |
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Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatmentParacoccidioidomycosisMonocyte subsetsPulmonary fibrosisAntifungal therapyBackground: Paracoccidioidomycosis (PCM) is systemic mycosis caused by the thermal dimorphic fungus of genus Paracoccidioides, leading to either acute/subacute (AF) or chronic (CF) clinical forms. Numerous CF patients after treatment exhibit sequels, such as pulmonary and adrenal fibrosis. Monocytes are cells that are involved in the inflammatory response during active infection as well as in the fibrogenesis. These cells comprise a heterogeneous population with distinct phenotypic and functional activities. The scope of this study was to identify changes regarding functional and phenotypical aspects in monocytes comparing CF PCM patients on antifungal treatment versus non-treated patients (PMC-p).Methods: Twenty-three CF PCM composed of 11 non-treated patients (NTG) and 12 patients in apparent cure (ACG) were studied. Sixteen healthy individuals were used as control group (CG). Monocyte subsets were determined by immunophenotyping based on CD14 and CD16 expression. Cellular function was measured in vitro with and without stimulation with lipopolysaccharide (LPS) and P. brasiliensis exoantigen (PbAg) for 24 hours. Independent samples were compared using unpaired t tests, dependent samples were analyzed by paired t-test. Groups of more than two independent samples were analyzed using an ANOVA, with Tukey's post-test. Significance was set up at p < 0.05.Results: Our results showed high counts of peripheral blood CD14(+)CD16(+) and CD14(+)CD16(++) monocytes in untreated PCM-p accompanied by intense production of pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and profibrotic growth factors (TGF-beta 1 and bFGF) by monocytes challenged with P. brasiliensis antigens. After the introduction of antifungal therapy, the counts of CD14(+)CD16(+) cells returned to baseline while CD14(+)CD16(++) counts remained high. Interestingly, counts of CD14(+)CD16(++) monocytes remained elevated even 52 +/- 7 months after successful antifungal treatment. Furthermore, the ACG-patients showed preserved pro-inflammatory activity in the presence of specific antigen stimuli and high spontaneous production of TNF-a by monocytes.Conclusions: Infection with Paracoccidioides leads to initiation of a specific proinflammatory response by monocytes of PCM-p during active disease and in the apparent cure. A profibrotic profile by monocytes was observed only at admission. Furthermore, PCM-p with apparent cure showed high spontaneous production of TNF-alpha and high counts of CD14(+)CD16(++) monocytes, probably induced by hypoxia duo to fibrotic sequelae.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Estadual Paulista, UNESP, Fac Med Botucatu, BR-18618970 Botucatu, SP, BrazilUniv Estadual Paulista, UNESP, Dept Ciencias Biol, Fac Ciencias,Lab Imunopatol Expt LIPE, BR-17047001 Bauru, SP, BrazilUniv Estadual Paulista, UNESP, Fac Med Botucatu, BR-18618970 Botucatu, SP, BrazilUniv Estadual Paulista, UNESP, Dept Ciencias Biol, Fac Ciencias,Lab Imunopatol Expt LIPE, BR-17047001 Bauru, SP, BrazilFAPESP: 09/51105-1Biomed Central LtdUniversidade Estadual Paulista (Unesp)Venturini, James [UNESP]Cavalcante, Ricardo Souza [UNESP]Golim, Marjorie de Assis [UNESP]Marchetti, Camila Martins [UNESP]Azevedo, Priscila Zacarias de [UNESP]Amorim, Barbara Casella [UNESP]Arruda, Maria Sueli Parreira de [UNESP]Mendes, Rinaldo Poncio [UNESP]2015-03-18T15:55:51Z2015-03-18T15:55:51Z2014-10-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://dx.doi.org/10.1186/s12879-014-0552-xBmc Infectious Diseases. London: Biomed Central Ltd, v. 14, 9 p., 2014.1471-2334http://hdl.handle.net/11449/11733110.1186/s12879-014-0552-xWOS:000343830800001WOS000343830800001.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBmc Infectious Diseases2.6201,576info:eu-repo/semantics/openAccess2024-04-23T15:23:39Zoai:repositorio.unesp.br:11449/117331Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:36:04.038088Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
title |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
spellingShingle |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment Venturini, James [UNESP] Paracoccidioidomycosis Monocyte subsets Pulmonary fibrosis Antifungal therapy |
title_short |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
title_full |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
title_fullStr |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
title_full_unstemmed |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
title_sort |
Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment |
author |
Venturini, James [UNESP] |
author_facet |
Venturini, James [UNESP] Cavalcante, Ricardo Souza [UNESP] Golim, Marjorie de Assis [UNESP] Marchetti, Camila Martins [UNESP] Azevedo, Priscila Zacarias de [UNESP] Amorim, Barbara Casella [UNESP] Arruda, Maria Sueli Parreira de [UNESP] Mendes, Rinaldo Poncio [UNESP] |
author_role |
author |
author2 |
Cavalcante, Ricardo Souza [UNESP] Golim, Marjorie de Assis [UNESP] Marchetti, Camila Martins [UNESP] Azevedo, Priscila Zacarias de [UNESP] Amorim, Barbara Casella [UNESP] Arruda, Maria Sueli Parreira de [UNESP] Mendes, Rinaldo Poncio [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Venturini, James [UNESP] Cavalcante, Ricardo Souza [UNESP] Golim, Marjorie de Assis [UNESP] Marchetti, Camila Martins [UNESP] Azevedo, Priscila Zacarias de [UNESP] Amorim, Barbara Casella [UNESP] Arruda, Maria Sueli Parreira de [UNESP] Mendes, Rinaldo Poncio [UNESP] |
dc.subject.por.fl_str_mv |
Paracoccidioidomycosis Monocyte subsets Pulmonary fibrosis Antifungal therapy |
topic |
Paracoccidioidomycosis Monocyte subsets Pulmonary fibrosis Antifungal therapy |
description |
Background: Paracoccidioidomycosis (PCM) is systemic mycosis caused by the thermal dimorphic fungus of genus Paracoccidioides, leading to either acute/subacute (AF) or chronic (CF) clinical forms. Numerous CF patients after treatment exhibit sequels, such as pulmonary and adrenal fibrosis. Monocytes are cells that are involved in the inflammatory response during active infection as well as in the fibrogenesis. These cells comprise a heterogeneous population with distinct phenotypic and functional activities. The scope of this study was to identify changes regarding functional and phenotypical aspects in monocytes comparing CF PCM patients on antifungal treatment versus non-treated patients (PMC-p).Methods: Twenty-three CF PCM composed of 11 non-treated patients (NTG) and 12 patients in apparent cure (ACG) were studied. Sixteen healthy individuals were used as control group (CG). Monocyte subsets were determined by immunophenotyping based on CD14 and CD16 expression. Cellular function was measured in vitro with and without stimulation with lipopolysaccharide (LPS) and P. brasiliensis exoantigen (PbAg) for 24 hours. Independent samples were compared using unpaired t tests, dependent samples were analyzed by paired t-test. Groups of more than two independent samples were analyzed using an ANOVA, with Tukey's post-test. Significance was set up at p < 0.05.Results: Our results showed high counts of peripheral blood CD14(+)CD16(+) and CD14(+)CD16(++) monocytes in untreated PCM-p accompanied by intense production of pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and profibrotic growth factors (TGF-beta 1 and bFGF) by monocytes challenged with P. brasiliensis antigens. After the introduction of antifungal therapy, the counts of CD14(+)CD16(+) cells returned to baseline while CD14(+)CD16(++) counts remained high. Interestingly, counts of CD14(+)CD16(++) monocytes remained elevated even 52 +/- 7 months after successful antifungal treatment. Furthermore, the ACG-patients showed preserved pro-inflammatory activity in the presence of specific antigen stimuli and high spontaneous production of TNF-a by monocytes.Conclusions: Infection with Paracoccidioides leads to initiation of a specific proinflammatory response by monocytes of PCM-p during active disease and in the apparent cure. A profibrotic profile by monocytes was observed only at admission. Furthermore, PCM-p with apparent cure showed high spontaneous production of TNF-alpha and high counts of CD14(+)CD16(++) monocytes, probably induced by hypoxia duo to fibrotic sequelae. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-10-16 2015-03-18T15:55:51Z 2015-03-18T15:55:51Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/s12879-014-0552-x Bmc Infectious Diseases. London: Biomed Central Ltd, v. 14, 9 p., 2014. 1471-2334 http://hdl.handle.net/11449/117331 10.1186/s12879-014-0552-x WOS:000343830800001 WOS000343830800001.pdf |
url |
http://dx.doi.org/10.1186/s12879-014-0552-x http://hdl.handle.net/11449/117331 |
identifier_str_mv |
Bmc Infectious Diseases. London: Biomed Central Ltd, v. 14, 9 p., 2014. 1471-2334 10.1186/s12879-014-0552-x WOS:000343830800001 WOS000343830800001.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bmc Infectious Diseases 2.620 1,576 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd |
publisher.none.fl_str_mv |
Biomed Central Ltd |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129094389334016 |