Immunization with Ascaris suum Extract Impairs T Cell Functions in Mice

Ferreira, Ana Paula; Faquim, Eliana S.; Abrahamsohn, Ises A.; Macedo, Mahasti Sahihi de

doi:10.1006/cimm.1995.1070

Cited by 48 publications

(66 citation statements)

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“…In addition, the LN cells from the groups of mice injected with different doses of E-Asc did not secrete detectable IL-2 or IFN-g after in vitro restimulation with OA compared to the group immunized with OA alone, indicating a dramatic effect on these Th1-type cytokines. When these LN cells were restimulated with E-Asc, the profile of cytokines detected in cell cultures was similar to that obtained after immunization with A. suum extract prepared from adult worms (15). The highest dose of EAsc, which was more suppressive, induced more IL-4 and less IL-2 and IFN-g, whereas the opposite was true for the lowest dose that was less suppressive.…”

Section: Discussionsupporting

confidence: 52%

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties

Souza

Faquim-Mauro

Macedo

2002

Braz J Med Biol Res

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Adult Ascaris suum body extract (Asc) prepared from male and female worms (with stored eggs) down-regulates the specific immune response of DBA/2 mice to ovalbumin (OA) and preferentially stimulates a Th2 response to its own components, which is responsible for the suppression of the OA-specific Th1 response. Here, we investigated the participation of soluble extracts prepared from male or female worms or from eggs (E-Asc) in these immunological events. Extracts from either sex (1 mg/animal) or E-Asc (0.35 or 1 mg protein/ animal) suppressed the delayed-type hypersensitivity (DTH) reaction (60-85%), proliferative response (50-70%), IL-2 and IFN-g secretion (below detection threshold) and IgG1 antibody production (70-90%) of DBA/2 mice to OA. A dose of 0.1 mg E-Asc/animal did not change DTH or proliferation, but was as effective as 0.35 mg in suppressing IL-2 and IFN-g, and OA-specific IgG1 antibodies. Lymph node cells from DBA/2 mice injected with Asc (1 mg/animal) or a high dose of E-Asc (1 mg protein/animal) secreted IL-4 upon in vitro stimulation with concanavalin A. As previously demonstrated for Asc, the cytokine profile obtained with the E-Asc was dose dependent and changed towards Th1 when a low dose (0.1 mg protein/animal) was used. Taken together, these results suggest that adult worms of either sex and eggs induce the same type of T cell response and share similar immunosuppressive properties.

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Section: Discussionsupporting

confidence: 52%

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties

Souza

Faquim-Mauro

Macedo

2002

Braz J Med Biol Res

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“…On the other hand, in vitro neutralization of IL-4 and IL-10 did not change the proliferative hyporesponsiveness and the low cytokine secretion by OVA-specific T cells obtained from mice immunized with OVA+Asc [17]. Using a limitingdilution assay, a low frequency of OVA-specific T cells was demonstrated in mice immunized with OVA+Asc [11]. These results suggest that Asc or PI exert their suppressive effect on the inductive phase of the immune response.…”

Section: Introductionmentioning

confidence: 77%

“…We have previously shown that Asc or PI have the same ability as a live infection to strongly suppress the immune response and to induce a typical Th2 response (with IL-4 and IL-10 secretion) which is responsible for the suppressive effect [10][11][12][13][14]. Concerning the mechanisms involved in this effect, we investigated in this work the hypothesis that PI components could act in the inductive phase of the immune response, modulating the Ag presentation process by APC, and consequently T cell activation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Asc was prepared from adult A. suum bodies and fractionated by gel filtration under conditions previously described [11]. Fractions eluted in the first peak (PI) corresponding to high-molecular-weight components were concentrated with Centripep 100 (Amicon) concentrator (100 cut-off point).…”

Section: Antigens and Antibodiesmentioning

confidence: 99%

“…We have previously shown that an Ascaris suum extract (Asc) from adult worms, as well as its highmolecular-weight components (PI) obtained by gel filtration, inhibit the Th1-and Th2-related immune responses induced by immunization of mice with an unrelated Ag, OVA, such as delayed-type hypersensitivity reactions, antibody production, in vitro lymphoproliferative responses and cytokine secretion induced by in vitro stimulation with Ag or mitogen [11,12]. More recently, it was demonstrated that Asc also suppresses experimental allergic asthma in mice [13].…”

Section: Introductionmentioning

confidence: 99%

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Immunosuppressive components of Ascaris suum down‐regulate expression of costimulatory molecules and function of antigen‐presenting cells via an IL‐10‐mediated mechanism

et al. 2006

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High-molecular-weight components (PI) of Ascaris suum suppress both cell-mediated and humoral responses against ovalbumin (OVA) via an IL-4/IL-10-dependent mechanism. The aim of this work was to investigate the effect of PI on the ability of APC to activate T cells and the role of IL-10 in this process. Flow cytometry analyses of MHC class II, CD80, CD86 and CD40 molecules on LN cells from mice immunized with OVA or OVA+PI showed that PI inhibits expression of these molecules on unfractionated cells and on purified CD11c + cells. A low proliferative response was obtained when OVA-specific TCR-Tg T cells were incubated with CD11c + cells from OVA+PI-immunized mice pulsed with OVA, when compared to those incubated with cells from OVAimmunized mice. Similar results were obtained using as APC CD11c + cells from OVAimmunized mice pulsed with OVA+PI, which also expressed less of the four markers. The inhibitory effect of PI on both the expression of costimulatory molecules and the induction of T cell proliferation was abolished in IL-10-deficient mice. Our data indicate that the potent immunosuppressive effect of A. suum extract components on the host immune system is primarily related to their property of down-regulating the Agpresenting ability of DC via an IL-10-mediated mechanism.

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Impairment of dendritic cell function by excretory‐secretory products: A potential mechanism for nematode‐induced immunosuppression

et al. 2007

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To determine whether helminth-derived products modulate dendritic cell (DC) function, we investigated the effects of excretory-secretory products (ES) and adult worm homogenate (AWH) derived from the gastrointestinal nematode Heligmosomoides polygyrus (Hp) on murine bone marrow-derived DC (BMDC). Compared to the TLR9 ligand CpG, Hp-derived products alone failed to induce DC activation. ES, but not AWH, inhibited BMDC cytokine and chemokine production and co-stimulatory molecule expression (CD40, CD86 and MHC class II) induced by TLR ligation. TLR ligand-independent, PMA-induced DC activation was unaffected by ES. Recipients of ES-treated BMDC pulsed with OVA had suppressed Ab responses in vivo, irrespective of the Th1 or Th2 isotype affiliation, compared to recipients of control OVA-pulsed BMDC. Importantly, suppression occurred even in the presence of the potent type 1 adjuvant CpG. In contrast to untreated OVA-pulsed BMDC, ES-treated BMDC pulsed with OVA had reduced co-stimulatory molecule and cytokine expression. CD4 + CD25 + Foxp3 -T cells, which secreted high IL-10 levels, were generated in co-cultures of OT-II OVAspecific TCR-transgenic CD4 + T cells and ES-treated BMDC. These IL-10-secreting T cells suppressed effector CD4 + T cell proliferation and IFN-c production, the latter effect mediated by an IL-10-dependent mechanism. Together, these results demonstrate that nematode ES impaired DC function and suppressed both Th1 and Th2 adaptive immune responses possibly by inducing regulatory T cells.

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Immunization with Ascaris suum Extract Impairs T Cell Functions in Mice

Cited by 48 publications

References 0 publications

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties

Immunosuppressive components of Ascaris suum down‐regulate expression of costimulatory molecules and function of antigen‐presenting cells via an IL‐10‐mediated mechanism

Impairment of dendritic cell function by excretory‐secretory products: A potential mechanism for nematode‐induced immunosuppression

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