Regulatory cells induced by acute toxoplasmosis prevent the development of allergic lung inflammation

Fenoy, Ignacio Martín; Sánchez, Vanesa Roxana; Soto, Ariadna Soledad; Picchio, Mariano S.; Maglioco, Andrea; Corigliano, Mariana G.; Dran, Graciela; Martin, Valentina; Goldman, Alejandra

doi:10.1016/j.imbio.2014.11.016

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…gondii infection suppressed Th2-related inflammation in a mouse model of birch-pollen-induced allergic airway inflammation [ 16 ]. These results were confirmed by Fenoy et al [ 17 , 18 ] further describing a major role for regulatory T cells in thoracic lymph nodes of T . gondii -infected mice in preventing allergic lung inflammation in their model.…”

Section: Introductionsupporting

confidence: 79%

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Oocyst-Derived Extract of Toxoplasma Gondii Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy

et al. 2016

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IntroductionPreviously, we have shown that oral infection with Toxoplasma gondii oocysts prevented type I allergy in mice. Here we investigated whether the application of a T. gondii oocyst lysate antigen (OLA) could also reduce allergy development. BALB/c mice were immunised twice with OLA followed by sensitisation with the major birch pollen (BP) allergen Bet v 1 and an aerosol challenge with BP extract.MethodsFirst, we tested OLA in vitro. Stimulation of splenocytes and bone marrow-derived dendritic cells (BMDC) with OLA led to the production of pro-inflammatory and regulatory cytokines such as IL-6, IFN-γ and IL-10. Moreover, BMDC exposed to OLA upregulated the maturation markers CD40, CD80, CD86, and MHCII. Furthermore, OLA was recognised by TLR2-transfected human embryonic kidney cells.ResultsImmunisation of mice with OLA induced high levels of Toxoplasma-specific IgG antibodies in sera along with increased production of IFN-γ and IL-10 in Toxoplasma-antigen restimulated splenocytes. OLA reduced allergic airway inflammation as manifested by significant reduction of eosinophils in bronchoalveolar fluids, decreased cellular infiltrates and mucus production in the lungs. Accordingly, Bet v 1-specific IgE was decreased in OLA-pretreated mice. The reduced allergic immune responses were accompanied by increased numbers of CD4+CD25highFoxp3+ regulatory T cells in spleens as well as by increased numbers of granulocytic myeloid-derived suppressor cells in lungs when compared to sensitised controls suggesting that these two cell populations might be involved in the suppression of the allergic immune responses.ConclusionOur data demonstrate that pretreatment with the oocyst extract can exert anti-allergic effects comparable to T. gondii infection. Thus, the immunomodulatory properties of the parasite extract indicate that this extract and in the future defined molecules thereof might serve as immunomodulatory adjuvants in allergy treatment and prophylaxis.

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Section: Introductionsupporting

confidence: 79%

“…The expansion of regulatory T cells in thoracic lymph nodes after infection with T . gondii was recently described, also showing that adoptive transfer of these cells resulted in suppression of allergic airway inflammation [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Oocyst-Derived Extract of Toxoplasma Gondii Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy

et al. 2016

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“…This suggests that IL-10 is not a key cytokine involved in TLA-induced allergy prevention and this is in agreement with findings by Fenoy et al ., who could show that T . gondii -induced suppression of allergy is IL-10-independent 47 . We have previously shown that decreased levels of antigen-specific IL-10 in cell cultures could be explained by increased uptake via upregulated IL-10 receptor 48 .…”

Section: Discussionmentioning

confidence: 96%

Toxoplasma gondii tachyzoite-extract acts as a potent immunomodulator against allergic sensitization and airway inflammation

Drinić

Wagner

Sarate

et al. 2017

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Epidemiological and experimental studies have shown an inverse relationship between infections with certain parasites and a reduced incidence of allergic diseases. We and others have shown that infection with Toxoplasma gondii prevents the development of allergy in mice. To establish whether this beneficial effect could be recapitulated by soluble products of this parasite, we tested an extract derived from T. gondii tachyzoites. Immunization of BALB/c mice with tachyzoites lysate antigen (TLA) elicited mixed Th1/Th2 responses. When TLA was applied together with the sensitizing ovalbumin (OVA), the development of allergic airway inflammation was reduced, with decreased airway hyperresponsiveness associated with reduced peribronchial and perivascular cellular infiltration, reduced production of OVA-specific Th2 cytokines in lungs and spleens and reduced levels of serum OVA-specific IgG1 as well as IgE-dependent basophil degranulation. Of note, TLA retained its immunomodulatory properties, inducing high levels of IL-6, TNFα, IL-10 and IL-12p70 in bone marrow-derived dendritic cells after heat-inactivation or proteinase K-treatment for disruption of proteins, but not after sodium metaperiodate-treatment that degrades carbohydrate structures, suggesting that carbohydrates may play a role in immunomodulatory properties of TLA. Here we show that extracts derived from parasites may replicate the benefits of parasitic infection, offering new therapies for immune-mediated disorders.

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“…gondii infection strongly diminish the development of an allergic airway inflammation [ 33 ]. The mechanisms behind this phenomenon included the deviation to a Th1 phenotype plus the induction of regulatory cells [ 37 , 38 ] that might result from the activity of many different immunomodulatory proteins.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy

et al. 2017

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Serine-proteases are important players in the pathogenesis of asthma, promoting inflammation and tissue remodeling. It’s also known that many serine protease inhibitors display immunomodulatory properties. TgPI-1 is a Toxoplasma gondii protein that exhibits broad spectrum inhibitory activity against serine proteases. In view of the increased prevalence of atopic disorders and the need to develop new treatment strategies we sought to investigate the potential of TgPI-1 for treating respiratory allergies. For this purpose, we developed a therapeutic experimental model. BALB/c mice were rendered allergic by intraperitoneal ovalbumin-alum sensitization and airway-challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with rTgPI-1 alone or with a mixture of rTgPI-1 and ovalbumin (OVA). A week later mice were given a secondary aerosol challenge. Treatment with rTgPI-1 alone or co-administered with OVA diminished bronchoalveolar eosinophilia, mucus production and peribronchial lung infiltration. This effect was accompanied by a lung resistance reduction of 26.3% and 50.3% respectively. Both treatments resulted in the production of lower levels of IL-4, IL-5, IFN-γ and regulatory IL-10 by thoracic lymph node cells stimulated with OVA. Interestingly, significant decreases in OVA specific IgE and T cell proliferation, and increases in FoxP3+ T cells at local and systemic levels were only detected when the inhibitor was administered along with OVA. These results show that both rTgPI-1 treatments reduced asthma hallmarks. However, co-administration of the inhibitor with the allergen was more effective. Hence, rTgPI-1 emerges as a novel adjuvant candidate for asthma treatment.

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Regulatory cells induced by acute toxoplasmosis prevent the development of allergic lung inflammation

Cited by 5 publications

References 36 publications

Oocyst-Derived Extract of Toxoplasma Gondii Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy

Oocyst-Derived Extract of Toxoplasma Gondii Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy

Toxoplasma gondii tachyzoite-extract acts as a potent immunomodulator against allergic sensitization and airway inflammation

Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy

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