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

Silva, Sandriana R.; Jacysyn, Jacqueline F.; Macedo, Mahasti Sahihi de; Faquim-Mauro, Eliana L.

doi:10.1002/eji.200636110

Cited by 36 publications

(34 citation statements)

References 48 publications

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“…Surprisingly, the A. suum extract decreased IL-10 levels to below detection limits in naïve rats as well as in both rats and mice subjected to ZYA. This is intriguing, since high-molecular-weight components of this extract were shown to downregulate the presentation of antigens by dendritic cells via an IL-10-dependent mechanism (28). The fact that we measured IL-10 levels in vivo, whereas the results from reference 28 were obtained in vitro, may explain this discrepancy.…”

Section: Vol 76 2008 Helminth Protection In Immune Arthritis 2743mentioning

confidence: 72%

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Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models

Rocha¹,

Leite²,

Pompeu

et al. 2008

Infect Immun

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We investigated the effect of an extract from a helminth (Ascaris suum) in zymosan-induced arthritis (ZYA) or collagen-induced arthritis (CIA). Rats and mice, respectively, received 1 mg and 0.1 mg zymosan intraarticularly (i.a.). Test groups received an A. suum extract either per os (p.o.) or intraperitoneally (i.p.) 30 min prior to i.a. zymosan. Controls received saline. Hypernociception was measured using the articular incapacitation test. Cell influx, nitrite, and cytokine levels were assessed in joint exudates. The synovia and distal femoral extremities were used for histopathology. Cartilage damage was assessed through determining glycosaminoglycan (GAG) content. DBA/1J mice were subjected to CIA. The test group received A. suum extract i.p. 1 day after CIA became clinically detectable. Clinical severity and hypernociception were assessed daily. Neutrophil influx was determined using myeloperoxidase activity. The A. suum extract, either i.p. or p.o., significantly and dose-dependently inhibited cell influx and hypernociception in ZYA in addition to reducing GAG loss and ameliorating synovitis. The A. suum extract reduced i.a. levels of NO, interleukin-1␤ (IL-1␤), and IL-10 but not tumor necrosis factor alpha (TNF-␣) in rats subjected to ZYA while reducing i.a. IL-10, but not IL-1␤ or TNF-␣, levels in mice. Clinically, mice subjected to CIA treated with the A. suum extract had less severe arthritis. Hypernociception, myeloperoxidase activity, and synovitis severity were significantly reduced. These data show that a helminth extract given p.o. protects from arthritis severity in two classical arthritis models. This A. suum effect is species independent and functions orally and parenterally. The results show clinical and structural benefits when A. suum extract is given either prophylactically or therapeutically.

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Section: Vol 76 2008 Helminth Protection In Immune Arthritis 2743mentioning

confidence: 72%

“…Using mice sensitized to ovalbumin, it has been demonstrated that the A. suum crude extract, prepared as used in the present study, or its affinitypurified high-molecular-weight components are able to downmodulate the antigen-processing ability of dendritic cells (28). Results represent means Ϯ SEM (n ϭ 6 animals for each group).…”

Section: Discussionmentioning

confidence: 86%

Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models

Rocha¹,

Leite²,

Pompeu

et al. 2008

Infect Immun

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“…A. suum re- 12 leases potent immunosuppressive molecules that interfere with antigen presentation of dendritic cells [60] . The purified proteins maintain their ability to inhibit T-cell-dependent antibody production and to suppress both Th1 and Th2 responses through modulation of IL-4 and IL-10 [61] .…”

Section: Immune Responses To Ascarismentioning

confidence: 99%

Ascaris lumbricoides: A Review of Its Epidemiology and Relationship to Other Infections

Scott¹

2008

Ann Nestlé [Engl]

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This review highlights advances made since 2004 in understanding the epidemiology of infection and the interactions between Ascarislumbricoides and other concurrent infections. As water scarcity increases, untreated wastewater is increasingly used to irrigate crops, thus increasing the risk of transmission. New methods to detect and inactivate Ascaris eggs in water, soil and food are described. The association between pig ownership and Ascaris infection in humans may represent cross-transmission as hybridization among the pig and human ascarids occurs more frequently than previously believed. Geospatial analyses have successfully predicted infection levels both at a regional level (based on vegetation indices, temperature and humidity) and within communities (based on social and environmental factors). The interpretation of antibody and cytokine responses to Ascaris is becoming clearer, as researchers recognize the role of antigen type, age, the history of Ascaris and other infections. The considerable interest emerging on the interactions between Ascaris and other infections (helminths, malaria, HIV, tuberculosis) and allergy is explored. The impact of concurrent infection on the design of control strategies is discussed including the benefits arising from combination therapies and the evidence that intestinal nematodes impair the efficacy of childhood vaccines. Finally, recommended areas for future research are identified.

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“…It has been shown that PI downregulates the expression of costimulatory agents (CD40, CD80 and CD86) and major histocompatibility complex II molecules on the surface of dendritic cells and, consequently, reduces the antigen-presenting function of these cells. This effect was mediated by IL-10 16 . IFN-γ and IL-10 have opposite effects on immune system activation 10 .…”

Section: Figurementioning

confidence: 88%

Boosting the suppressive effects of Ascaris suum components in IFN-γ-deficient mice

Souza

Macedo

2009

Rev. Soc. Bras. Med. Trop.

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High molecular weight components from Ascaris suum extract suppress ovalbumin-specific immunity in mice. In IFN-γ-deficient mice, ovalbuminspecific delayed-type hypersensitivity reactions are more strongly downregulated by these suppressive components. Here, the cellularity of the delayed-type hypersensitivity reaction in IFN-γ-deficient mice and the increased downregulation induced by Ascaris suum components were analyzed. IL-12p40-dependent neutrophilic influx was predominant. Suboptimal doses of the suppressive fraction from this nematode completely inhibited the hypersensitivity reaction, thus indicating intensification of the immunosuppression under conditions of intense recruitment of IFN-γ-independent neutrophils. Key-words:Ascaris suum. Delayed-type hypersensitivity. Immunosuppression. IFN-γ-deficient mice. Neutrophil. RESUMOComponentes de alto peso molecular do extrato de Ascaris suum suprimem a imunidade específica à ovalbumina em camundongos. Em camundongos geneticamente deficientes de IFN-γ a reação de hipersensibilidade tardia específica para ovalbumina foi mais fortemente prejudicada por estes componentes supressivos. Aqui, a celularidade da reação de hipersensibilidade tardia em camundongos deficientes de IFN-γe o incremento na supressão induzida por componentes do Ascaris suum foram analisados. Influxo neutrofílico, dependente de IL-12p40, foi predominante. Dose subótima da fração supressiva do nematódeo inibiu completamente a reação de hipersensibilidade, indicando uma intensificação da imunossupressão em condições de recrutamento intenso de neutrófilos independente de IFN-γ.  Palavras-chaves: Ascaris suum. Hipersensibilidade tardia. Imunossupressão. Camundongos deficientes em IFN-γ. Neutrófilos.

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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

Cited by 36 publications

References 48 publications

Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models

Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models

<i>Ascaris lumbricoides</i>: A Review of Its Epidemiology and Relationship to Other Infections

Boosting the suppressive effects of Ascaris suum components in IFN-γ-deficient mice

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