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Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.

Fujiwara RT, Cançado GG, Freitas PA, Santiago HC, Massara CL, Dos Santos Carvalho O, Corrêa-Oliveira R, Geiger SM, Bethony J - PLoS Negl Trop Dis (2009)

Bottom Line: These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR.The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected-derived mDCs was further evidenced by their reduced ability to induce cell proliferation.Chronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the ablation of the parasite-specific T cell proliferative response.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Immunology, Instituto René Rachou, Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT

Background: Hookworms survive for several years (5 to 7 years) in the host lumen, inducing a robust but largely ineffective immune response. Among the most striking aspects of the immune response to hookworm (as with many other helminths) is the ablation of parasite-specific T cell proliferative response (hyporesponsiveness). While the role of the adaptive immune response in human helminth infection has been well investigated, the role of the innate immune responses (e.g., dendritic cells and eosinophils) has received less attention and remains to be clearly elucidated.

Methodology/principal findings: We report on the differentiation/maturation of host dendritic cells in vitro and the eosinophil activation/function associated with human hookworm infection. Mature DCs (mDCs) from Necator americanus (Necator)-infected individuals showed an impaired differentiation process compared to the mDCs of non-infected individuals, as evidenced by the differential expression of CD11c and CD14. These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR. The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected-derived mDCs was further evidenced by their reduced ability to induce cell proliferation. We also showed that this alternative DC differentiation is partially induced by excreted-secreted hookworm products. Conversely, eosinophils from the same individuals showed a highly activated status, with an upregulation of major cell surface markers. Antigen-pulsed eosinophils from N. americanus-infected individuals induced significant cell proliferation of autologous PBMCs, when compared to non-infected individuals.

Conclusion: Chronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the ablation of the parasite-specific T cell proliferative response. Interestingly, a concomitant upregulation of the major cell surface markers of eosinophils was observed in hookworm-infected individuals, indicative of antigen-specific immune responses, especially antigen presentation. We showed that in addition to the postulated role of the eosinophils as effector cells against helminth infection, activated cells may also be recruited to sites of inflammation and contribute to the immune response acting as antigen presenting cells.

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Related in: MedlinePlus

Flow cytometric analysis of monocyte-derived dendritic cell surface markers.(A) Analysis of dendritic cell differentiation/maturation (CD11c and CD14) and (B) expression of IgG receptor (CD16, FcγRIII). (C) Expression of co-stimulatory molecules. (D) Expression of cell presentation molecules. Median intensity of fluorescence is indicated on x axis (arbitrary units). Statistical differences are indicated in each graph with the significant P values.
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pntd-0000399-g001: Flow cytometric analysis of monocyte-derived dendritic cell surface markers.(A) Analysis of dendritic cell differentiation/maturation (CD11c and CD14) and (B) expression of IgG receptor (CD16, FcγRIII). (C) Expression of co-stimulatory molecules. (D) Expression of cell presentation molecules. Median intensity of fluorescence is indicated on x axis (arbitrary units). Statistical differences are indicated in each graph with the significant P values.

Mentions: Analysis of surface cell markers of monocyte-derived dendritic cells showed that DCs from Necator-infected individuals had an impaired differentiation process, as evidenced by the differential expression of CD11c and CD14 on the cell surface (Fig. 1A) compared to non-infected individuals. Differentiation of the monocytes into dendritic cells in non-infected individuals occurred as expected, with a relatively higher expression of CD11c and an absence lack of CD14 (Fig. 1A). However, dendritic cells from Necator-infected individuals showed a significantly lower expression of the immunoglobulin receptor CD16 (FcγRIII, P = 0.0177, Fig. 1B), the co-stimulatory molecule CD86 (P = 0.0025, Fig. 1C), and cell presentation molecules, such as CD1a (P = 0.0317), HLA-A, B, C and HLA-DR (P = 0.025 for both, Fig. 1D).


Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.

Fujiwara RT, Cançado GG, Freitas PA, Santiago HC, Massara CL, Dos Santos Carvalho O, Corrêa-Oliveira R, Geiger SM, Bethony J - PLoS Negl Trop Dis (2009)

Flow cytometric analysis of monocyte-derived dendritic cell surface markers.(A) Analysis of dendritic cell differentiation/maturation (CD11c and CD14) and (B) expression of IgG receptor (CD16, FcγRIII). (C) Expression of co-stimulatory molecules. (D) Expression of cell presentation molecules. Median intensity of fluorescence is indicated on x axis (arbitrary units). Statistical differences are indicated in each graph with the significant P values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654967&req=5

pntd-0000399-g001: Flow cytometric analysis of monocyte-derived dendritic cell surface markers.(A) Analysis of dendritic cell differentiation/maturation (CD11c and CD14) and (B) expression of IgG receptor (CD16, FcγRIII). (C) Expression of co-stimulatory molecules. (D) Expression of cell presentation molecules. Median intensity of fluorescence is indicated on x axis (arbitrary units). Statistical differences are indicated in each graph with the significant P values.
Mentions: Analysis of surface cell markers of monocyte-derived dendritic cells showed that DCs from Necator-infected individuals had an impaired differentiation process, as evidenced by the differential expression of CD11c and CD14 on the cell surface (Fig. 1A) compared to non-infected individuals. Differentiation of the monocytes into dendritic cells in non-infected individuals occurred as expected, with a relatively higher expression of CD11c and an absence lack of CD14 (Fig. 1A). However, dendritic cells from Necator-infected individuals showed a significantly lower expression of the immunoglobulin receptor CD16 (FcγRIII, P = 0.0177, Fig. 1B), the co-stimulatory molecule CD86 (P = 0.0025, Fig. 1C), and cell presentation molecules, such as CD1a (P = 0.0317), HLA-A, B, C and HLA-DR (P = 0.025 for both, Fig. 1D).

Bottom Line: These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR.The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected-derived mDCs was further evidenced by their reduced ability to induce cell proliferation.Chronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the ablation of the parasite-specific T cell proliferative response.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Immunology, Instituto René Rachou, Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT

Background: Hookworms survive for several years (5 to 7 years) in the host lumen, inducing a robust but largely ineffective immune response. Among the most striking aspects of the immune response to hookworm (as with many other helminths) is the ablation of parasite-specific T cell proliferative response (hyporesponsiveness). While the role of the adaptive immune response in human helminth infection has been well investigated, the role of the innate immune responses (e.g., dendritic cells and eosinophils) has received less attention and remains to be clearly elucidated.

Methodology/principal findings: We report on the differentiation/maturation of host dendritic cells in vitro and the eosinophil activation/function associated with human hookworm infection. Mature DCs (mDCs) from Necator americanus (Necator)-infected individuals showed an impaired differentiation process compared to the mDCs of non-infected individuals, as evidenced by the differential expression of CD11c and CD14. These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR. The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected-derived mDCs was further evidenced by their reduced ability to induce cell proliferation. We also showed that this alternative DC differentiation is partially induced by excreted-secreted hookworm products. Conversely, eosinophils from the same individuals showed a highly activated status, with an upregulation of major cell surface markers. Antigen-pulsed eosinophils from N. americanus-infected individuals induced significant cell proliferation of autologous PBMCs, when compared to non-infected individuals.

Conclusion: Chronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the ablation of the parasite-specific T cell proliferative response. Interestingly, a concomitant upregulation of the major cell surface markers of eosinophils was observed in hookworm-infected individuals, indicative of antigen-specific immune responses, especially antigen presentation. We showed that in addition to the postulated role of the eosinophils as effector cells against helminth infection, activated cells may also be recruited to sites of inflammation and contribute to the immune response acting as antigen presenting cells.

Show MeSH
Related in: MedlinePlus