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Monocyte-derived dendritic cells from patients with dermatophytosis restrict the growth of Trichophyton rubrum and induce CD4-T cell activation.

Santiago K, Bomfim GF, Criado PR, Almeida SR - PLoS ONE (2014)

Bottom Line: Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi.The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor.The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.

ABSTRACT
Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi. Trichophyton rubrum is the most common pathogen causing dermatophytosis. The immunology of dermatophytosis is currently poorly understood. Recently, our group investigated the interaction of T. rubrum conidia with peritoneal mouse macrophages. We found that macrophages phagocytose T. rubrum conidia resulted in a down-modulation of class II major histocompatibility complex (MHC) antigens and in the expression of co-stimulatory molecules. Furthermore, it induced the production of IL-10, and T. rubrum conidia differentiated into hyphae that grew and killed the macrophages after 8 hrs of culture. This work demonstrated that dendritic cells (DCs) and macrophages, from patients or normal individuals, avidly interact with pathogenic fungus T. rubrum. The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor. In contrast macrophage has only mannose receptor that participates in the phagocytosis or bound process. Another striking aspect of this study is that unlike macrophages that permit rapid growth of T. rubrum, human DC inhibited the growth and induces Th activation. The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response.

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Proliferation of CD4+ T-cell in presence of T. rubrum conidea-pulsed DCs from patients or non-infected individuals.On day 7, DCs were pulsed with or without conidia of T.rubrum (rate conidia/cell = 3∶1) by 24 hr. After, pulsed DCs were plated at 2×104 in triplicate wells of a 96-well flat-bottom plate. Autologous CD4+ T-cell were added at 2×105 cells/well. Proliferation of CD4 T-cell was evaluated after 5 days by measuring [3H]thymidine uptake and results were expressed as counts per minutes (CPM). The results represent the mean ± SD of three independents experiments, where the blood was collected from each study subjects (10 patients and 10 controls). As negative control was used only CD4+ T-cell and the result of proliferation was <100 cpm. Each dot correspond to an individual. *p<0.05 was considerate significant.
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pone-0110879-g004: Proliferation of CD4+ T-cell in presence of T. rubrum conidea-pulsed DCs from patients or non-infected individuals.On day 7, DCs were pulsed with or without conidia of T.rubrum (rate conidia/cell = 3∶1) by 24 hr. After, pulsed DCs were plated at 2×104 in triplicate wells of a 96-well flat-bottom plate. Autologous CD4+ T-cell were added at 2×105 cells/well. Proliferation of CD4 T-cell was evaluated after 5 days by measuring [3H]thymidine uptake and results were expressed as counts per minutes (CPM). The results represent the mean ± SD of three independents experiments, where the blood was collected from each study subjects (10 patients and 10 controls). As negative control was used only CD4+ T-cell and the result of proliferation was <100 cpm. Each dot correspond to an individual. *p<0.05 was considerate significant.

Mentions: As showed above that DCs were resistant to death by conidia, we assess whether the antigen presenting properties were preserved. DCs were prepared as described above and incubating (24 h) with conidia of T. rubrum (rate conidia/cell = 3∶1). The results showed that DCs incubated with conidea, were able to process and present antigen from the fungus and induce autologous T-cell proliferation in patients, but not in healthy non-immune individuals (Figure 4). The results indicate the specifity of the response, because T-cells from healthy individual did not proliferate in presence of dendritic cells. To analize the pattern of cytokine production by the CD4 cells, IL-4, IL-10 and IFN-γ were quantified. The results showed production of all cytokine tested, indicating that dendritic cells in presence of T. rubrum was not able to induce the predominance of Th1 (IFN-γ) neitheir Th2 (IL-10 and IL-4) response (Figure 5).


Monocyte-derived dendritic cells from patients with dermatophytosis restrict the growth of Trichophyton rubrum and induce CD4-T cell activation.

Santiago K, Bomfim GF, Criado PR, Almeida SR - PLoS ONE (2014)

Proliferation of CD4+ T-cell in presence of T. rubrum conidea-pulsed DCs from patients or non-infected individuals.On day 7, DCs were pulsed with or without conidia of T.rubrum (rate conidia/cell = 3∶1) by 24 hr. After, pulsed DCs were plated at 2×104 in triplicate wells of a 96-well flat-bottom plate. Autologous CD4+ T-cell were added at 2×105 cells/well. Proliferation of CD4 T-cell was evaluated after 5 days by measuring [3H]thymidine uptake and results were expressed as counts per minutes (CPM). The results represent the mean ± SD of three independents experiments, where the blood was collected from each study subjects (10 patients and 10 controls). As negative control was used only CD4+ T-cell and the result of proliferation was <100 cpm. Each dot correspond to an individual. *p<0.05 was considerate significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4220947&req=5

pone-0110879-g004: Proliferation of CD4+ T-cell in presence of T. rubrum conidea-pulsed DCs from patients or non-infected individuals.On day 7, DCs were pulsed with or without conidia of T.rubrum (rate conidia/cell = 3∶1) by 24 hr. After, pulsed DCs were plated at 2×104 in triplicate wells of a 96-well flat-bottom plate. Autologous CD4+ T-cell were added at 2×105 cells/well. Proliferation of CD4 T-cell was evaluated after 5 days by measuring [3H]thymidine uptake and results were expressed as counts per minutes (CPM). The results represent the mean ± SD of three independents experiments, where the blood was collected from each study subjects (10 patients and 10 controls). As negative control was used only CD4+ T-cell and the result of proliferation was <100 cpm. Each dot correspond to an individual. *p<0.05 was considerate significant.
Mentions: As showed above that DCs were resistant to death by conidia, we assess whether the antigen presenting properties were preserved. DCs were prepared as described above and incubating (24 h) with conidia of T. rubrum (rate conidia/cell = 3∶1). The results showed that DCs incubated with conidea, were able to process and present antigen from the fungus and induce autologous T-cell proliferation in patients, but not in healthy non-immune individuals (Figure 4). The results indicate the specifity of the response, because T-cells from healthy individual did not proliferate in presence of dendritic cells. To analize the pattern of cytokine production by the CD4 cells, IL-4, IL-10 and IFN-γ were quantified. The results showed production of all cytokine tested, indicating that dendritic cells in presence of T. rubrum was not able to induce the predominance of Th1 (IFN-γ) neitheir Th2 (IL-10 and IL-4) response (Figure 5).

Bottom Line: Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi.The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor.The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.

ABSTRACT
Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi. Trichophyton rubrum is the most common pathogen causing dermatophytosis. The immunology of dermatophytosis is currently poorly understood. Recently, our group investigated the interaction of T. rubrum conidia with peritoneal mouse macrophages. We found that macrophages phagocytose T. rubrum conidia resulted in a down-modulation of class II major histocompatibility complex (MHC) antigens and in the expression of co-stimulatory molecules. Furthermore, it induced the production of IL-10, and T. rubrum conidia differentiated into hyphae that grew and killed the macrophages after 8 hrs of culture. This work demonstrated that dendritic cells (DCs) and macrophages, from patients or normal individuals, avidly interact with pathogenic fungus T. rubrum. The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor. In contrast macrophage has only mannose receptor that participates in the phagocytosis or bound process. Another striking aspect of this study is that unlike macrophages that permit rapid growth of T. rubrum, human DC inhibited the growth and induces Th activation. The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response.

Show MeSH
Related in: MedlinePlus