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Modulation of allergic lung inflammation by adjuvants or by immunological tolerance

Abstract

Asthma is a complex syndrome with different phenotypes that share a common feature characterized by chronic inflammatory lung disease, airway hyper-reactivity, mucus hyper-secretion and elevated levels of IgE. Patients with allergic diseases appear to have a deregulated immune response to environmental stimulants. Classical asthma (type 2) exhibits airway eosinophilia associated with Th2 immunity whereas non classical asthma (type 1) is characterized by airway neutrophilia that can be associated with Th1 immunity. The hygiene hypothesis proposes that a reduced contact with infectious diseases increases the risk to develop allergic diseases. Infection acts as an adjuvant to the immune system because microbial products activate innate immunity via pattern recognition receptors (PRRs) such as Toll-like or NOD-like receptors. Engagement of these receptors influences the responses of adaptive immunity to environmental proteins that are involved in allergy. Nowadays, it is now known that certain allergens can act also as adjuvants. Our previous studies with microbes, microbial products or tolerance led us to postulate a non-classical view of the hygiene hypothesis that includes allergen-dependent and independent mechanisms. Specifically, we showed that signaling via TLR4, or recombinant BCG infection or mucosal tolerance attenuates asthma. The main objective of the project is to further dissect the molecular and cellular mechanisms involved in the induction and/or control of experimental asthma phenotypes (type 2 and 1). For this, the effect of exogenous, endogenous and allergen-derived adjuvants as well as recombinant BCG administered at different interval times, alone or in combination, will be investigated in the asthma model. Moreover, mucosal tolerance, induced in the absence of adjuvant and cross-tolerance will be also investigated. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BARROS, MICHELE S.; GOMES, ELIANE; GUERONI, DANIELE I.; RAMOS, ANDERSON D.; MIROTTI, LUCIANA; FLORSHEIM, ESTHER; BIZZARRO, BRUNA; LINO, CIRO N. R.; MACIEL, CERES; LINO-DOS-SANTOS-FRANCO, ADRIANA; TAVARES-DE-LIMA, WOTHAN; CAPURRO, MARGARETH L.; RUSSO, MOMTCHILO; SA-NUNES, ANDERSON. Exposure to iBites Induces a Mixed-Type Allergic Response following Salivary Antigens Challenge in Mice. PLoS One, v. 11, n. 5 MAY 20 2016. Web of Science Citations: 1.
LIGEIRO DE OLIVEIRA, ANA PAULA; SCHATZMANN PERON, JEAN PIERRE; SANTOS FRANCO, ADRIANA LINO; GOLEGA, BEATRIZ ACCETURI; VIEIRA, RODOLFO PAULA; MARTINEZ IBANEZ, OLGA CELIA; RIBEIRO, ORLANDO GARCIA; KOURY CABRERA, WAFA HANNA; DE FRANCO, MARCELO; OLIVEIRA-FILHO, RICARDO MARTINS; RIZZO, LUIZ VICENTE; VARGAFTIG, BERNARDO BORIS; DE LIMA, WOTHAN TAVARES. Ovariectomized OVA-Sensitized Mice Display Increased Frequency of CD4(+)Foxp3(+) T Regulatory Cells in the Periphery. PLoS One, v. 8, n. 6 JUN 17 2013. Web of Science Citations: 8.
LIGEIRO DE OLIVEIRA, ANA PAULA; LINO-DOS-SANTOS-FRANCO, ADRIANA; ACCETURI, BEATRIZ GOLEGA; HAMASATO, EDUARDO KENJI; MACHADO, ISABEL DAUFENBACK; GIMENES JUNIOR, JOAO ANTONIO; VIEIRA, RODOLFO DE PAULA; DAMAZO, AMILCAR SABINO; POLISELLI FARSKY, SANDRA HELENA; TAVARES-DE-LIMA, WOTHAN; PALERMO-NETO, JOAO. Long-term amphetamine treatment exacerbates inflammatory lung reaction while decreases airway hyper-responsiveness after allergic stimulus in rats. International Immunopharmacology, v. 14, n. 4, p. 523-529, DEC 2012. Web of Science Citations: 7.
LIGEIRO DE OLIVEIRA, ANA PAULA; LINO-DOS-SANTOS-FRANCO, ADRIANA; HAMASATO, EDUARDO KENJI; QUINTEIRO-FILHO, WANDERLEY; HEBEDA, CRISTINA BICHELS; DAMAZO, AMILCAR SABINO; POLISELLI FARSKY, SANDRA HELENA; TAVARES-DE-LIMA, WOTHAN; PALERMO-NETO, JOAO. Amphetamine modulates cellular recruitment and airway reactivity in a rat model of allergic lung inflammation. Toxicology Letters, v. 200, n. 1-2, p. 117-123, JAN 15 2011. Web of Science Citations: 14.
LIGEIRO DE OLIVEIRA, ANA PAULA; SCHATZMANN PERON, JEAN PIERRE; DAMAZO, AMILCAR SABINO; DOS SANTOS FRANCO, ADRIANA LINO; DOMINGOS, HELORI VANNI; OLIANI, SONIA MARIA; OLIVEIRA-FILHO, RICARDO MARTINS; VARGAFTIG, BERNARDO BORIS; TAVARES-DE-LIMA, WOTHAN. Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats. RESPIRATORY RESEARCH, v. 11, p. 115, 2010. Web of Science Citations: 15.

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