Activation/deactivation of macrophages and CD4+ T lymphocytes in experimental asthma

• Grant number: 04/14297-6
• Support type: Research Projects - Thematic Grants
• Duration: July 01, 2005 - December 31, 2009
• Field of knowledge: Biological Sciences - Immunology
• Principal researcher: Momtchilo Russo
• Grantee: Momtchilo Russo
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 05/00654-4 - Experimental asthma induced by Blomia tropicalis: modulation by immunological tolerance or by agonists of toll-like receptors 4, BP.PD

Abstract

Over the last 2 to 3 decades, the prevalence and severity of asthma and allergic disease has increased extensively in urban environments. The "hygiene hypothesis" was proposed in order to explain this increased incidence. This hypothesis is based on epidemiological evidence showing an inverse correlation between infections and allergic or autoimmune diseases. Recently, it was proposed that infections generate regulatory T cells that inhibit allergic (Th2) or autoimmune (Th1) diseases. Accordingly, the control of infectious diseases in urban environments decreased Treg cells activities that lead to a deregulated immune system. Various Treg cells has been characterized, natural Treg (CD4+ CD25+ CD45RB low) which inhibit aureactive T cells and adaptive Treg, that inhibit Th1- or Th2-mediated immune reactions. The adaptive Treg are heterogeneous cell population, but ali are CD4+ CD25+ and the majority expresses the transcription facto r Foxp3. One objective of the project is to investigate whether Treg induced by oral or nasal tolerance, or by recombinant BCG infection, or LPS would suppress the development of asthma. Another possibility for the suppression of asthma by infections is the emergence of activated macrophages. Recently, we have shown that i.v. administration of LPS suppresses established asthma. The suppressive activity was dependent on TLR4 and NOS2 expression and NO production. It is possible that other metabolites produced by activated macrophages such as those derived from indolamine, 2,3 dioxigenase or hemeoxigenase 1 pathways may also suppress asthma. For this purpose we will test some classical TLRs agonists (PIC, LPS or rBCG), or a synthetic TLR4-agonist on the development of asthma with focus on these metabolic pathway. (AU)

Scientific publications

(4)

(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)

CHRIST, ANA P.; RODRIGUEZ, DUNIA; BORTOLATTO, JULIANA; BORDUCCHI, ERICA; KELLER, ALEXANDRE; MUCIDA, DANIEL; SILVA, JOAO S.; LEITE, LUCIANA C. C.; RUSSO, MOMTCHILO. Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease. American Journal of Respiratory Cell and Molecular Biology, v. 43, n. 2, p. 243-252, AUG 2010. Web of Science Citations: 12.

MACIEL, MARCIA C. G.; FARIAS, JARDEL C.; MALUF, MICHELE J.; GOMES, ELIANE A.; PEREIRA, PAULO V. S.; ARAGAO-FILHO, WALMIR C.; FRAZAO, JOSIAS B.; COSTA, GRACIOMAR C.; SOUSA, SANARA M.; SILVA, LUCILENE A.; AMARAL, FLAVIA M. M.; RUSSO, MOMTCHILO; GUERRA, ROSANE N. M.; NASCIMENTO, FLAVIA R. F. Syzygium jambolanum treatment improves survival in lethal sepsis induced in mice. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, v. 8, OCT 13 2008. Web of Science Citations: 13.

BORTOLATTO, J.; BORDUCCHI, E.; RODRIGUEZ, D.; KELLER, A. C.; FAQUIM-MAURO, E.; BORTOLUCI, K. R.; MUCIDA, D.; GOMES, E.; CHRIST, A.; SCHNYDER-CANDRIAN, S.; SCHNYDER, B.; RYFFEL, B.; RUSSO, M. Toll-like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin-specific allergic airway disease: role of MyD88 adaptor molecule and interleukin-12/interferon-gamma axis. CLINICAL AND EXPERIMENTAL ALLERGY, v. 38, n. 10, p. 1668-1679, Oct. 2008. Web of Science Citations: 45.

COSTA-PINTO, FREDERICO AZEVEDO; BASSO, ALEXANDRE SALGADO; RUSSO, MOMTCHILO. Role of mast cell degranulation in the neural correlates of the immediate allergic reaction in a murine model of asthma. BRAIN BEHAVIOR AND IMMUNITY, v. 21, n. 6, p. 783-790, Aug. 2007.