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

<h4>Background</h4>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 cel...

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Autores principales:	Ricardo T Fujiwara, Guilherme G L Cançado, Paula A Freitas, Helton C Santiago, Cristiano Lara Massara, Omar Dos Santos Carvalho, Rodrigo Corrêa-Oliveira, Stefan M Geiger, Jeffrey Bethony
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/a92a407ffd56444583ca9950ee6209c3
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spelling	oai:doaj.org-article:a92a407ffd56444583ca9950ee6209c32021-11-25T06:32:56ZNecator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.1935-27271935-273510.1371/journal.pntd.0000399https://doaj.org/article/a92a407ffd56444583ca9950ee6209c32009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19308259/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusion</h4>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.Ricardo T FujiwaraGuilherme G L CançadoPaula A FreitasHelton C SantiagoCristiano Lara MassaraOmar Dos Santos CarvalhoRodrigo Corrêa-OliveiraStefan M GeigerJeffrey BethonyPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 3, Iss 3, p e399 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ricardo T Fujiwara Guilherme G L Cançado Paula A Freitas Helton C Santiago Cristiano Lara Massara Omar Dos Santos Carvalho Rodrigo Corrêa-Oliveira Stefan M Geiger Jeffrey Bethony Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusion</h4>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.
format	article
author	Ricardo T Fujiwara Guilherme G L Cançado Paula A Freitas Helton C Santiago Cristiano Lara Massara Omar Dos Santos Carvalho Rodrigo Corrêa-Oliveira Stefan M Geiger Jeffrey Bethony
author_facet	Ricardo T Fujiwara Guilherme G L Cançado Paula A Freitas Helton C Santiago Cristiano Lara Massara Omar Dos Santos Carvalho Rodrigo Corrêa-Oliveira Stefan M Geiger Jeffrey Bethony
author_sort	Ricardo T Fujiwara
title	Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
title_short	Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
title_full	Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
title_fullStr	Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
title_full_unstemmed	Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
title_sort	necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/a92a407ffd56444583ca9950ee6209c3
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Necator americanus infection: a possible cause of altered dendritic cell differentiation and eosinophil profile in chronically infected individuals.

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