title: Induction of CD4(+)CD25(+)FOXP3(+) regulatory T cells during human hookworm infection modulates antigen-mediated lymphocyte proliferation.
abstract: Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4(+)CD25(+)FOXP3(+) regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-β and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4(+)CD25(+)FOXP3(+) T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people.
authors.affiliation: Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Natasha Delaqua
authors.initials: ND
authors.lastname: Ricci
authors.forename: Jacqueline Araújo
authors.initials: JA
authors.lastname: Fiúza
authors.forename: Lilian Lacerda
authors.initials: LL
authors.lastname: Bueno
authors.forename: Guilherme Grossi Lopes
authors.initials: GG
authors.lastname: Cançado
authors.forename: Pedro Henrique
authors.initials: PH
authors.lastname: Gazzinelli-Guimarães
authors.forename: Virgillio Gandra
authors.initials: VG
authors.lastname: Martins
authors.forename: Leonardo Ferreira
authors.initials: LF
authors.lastname: Matoso
authors.forename: Rodrigo Rodrigues Cambraia
authors.initials: RR
authors.lastname: de Miranda
authors.forename: Stefan Michael
authors.initials: SM
authors.lastname: Geiger
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.forename: Andréa
authors.initials: A
authors.lastname: Gazzinelli
authors.forename: Daniella Castanheira
authors.initials: DC
authors.lastname: Bartholomeu
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000032:analysis; D006725:Hookworm Infections / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit
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