Evaluation of mechanisms involved in the modulation of immune response in a model of co-inflammation tuberculosis and allergy

• Grant number: 09/13689-1
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2010
• End date: March 31, 2012
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Vânia Luiza Deperon Bonato
• Grantee: Vânia Luiza Deperon Bonato
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

After repetitive exposition to allergen, the immune system generates immediate hypersensitivity response (type I) which involves the participation of IgE antibodies, mast cells, basophils, eosinophils and IL-4, IL-5 and IL-13 produced by CD4+ T lymphocytes. These are the essential elements of the immune system that characterize the allergic response. Animals immunized with heat killed Mycobacterium vaccae were protected against induction of allergic response in murine model of sensitization with ovalbumin. The down modulation of allergic response was also described in epidemiological and experimental studies employing the vaccine BCG (Bacillus Calmette-Guérin). In our laboratory, we have used mycobacterial antigens, released in a distinct way to the immune system, to down modulate the experimental asthma. Moreover, there are studies which described an inverse association referent to incidence of tuberculosis and allergy. The tuberculosis is also a disease of airways whose chronic character in susceptible individuals generates a very intense inflammation, which results in late hypersensitivity (type IV). Macrophages, dendritic cells, IFN-gamma producing-CD4+ and CD8+ T lymphocytes are important elements of protective immune response against tuberculosis. In this scenario, we have studied in a model of co-inflammation allergy and tuberculosis, the interference of one experimental disease in the progression of other and vice-versa. Our results show that independently of the infection by Mycobacterium tuberculosis precede (TB-OVA) or not (OVA-TB) the protocol of allergy induction, the allergic response is down modulated by infection. This down modulation mechanism seems to be dependent on interferon-gamma. However, the tuberculosis progresses in mice previously sensitized and challenged with OVA (OVA-TB), as we expected, but there is a decrease in the bacilli growth when mice are first infected and then submitted to the protocol of allergy (TB-OVA). In this context, this project is divided in two parts: 1- to investigate the role of interferon-gamma and IL-4 in the down modulation of allergic response and in the control of M. tuberculosis infection, respectively, using the model OVA-TB. For this strategy of investigation, the tools used will be mice deficient for the expression of IFN-gamma and depletion of IL-4 with antibodies against IL-4. The depletion but not mice deficient for the expression of IL-4 will be used because mice deficient for this cytokine do not develop immediate hypersensitivity; 2- Since leukotriens play a role in the immune response against experimental tuberculosis and in the allergic response, it is also our aim to evaluate whether leukotriens participate of the immune response associated with the decrease of bacilli growth in mice previously infected and submitted to the protocol of allergy induction. For this strategy of investigation, mice will be treated with the compound MK-886, which inhibits the synthesis of leukotriens, and in principle, mice deficient for the production of leukotriens will not be used because our hypothesis is that leukotriens secreted during allergy in the protocol TB-OVA play a role in the better control of M. tuberculosis infection compared to the mice infected (TB group). The results of this project which is based on the protocol of co-inflammation allergy and tuberculosis will relevant to define new immunological markers associated with protection or not in both diseases, besides to give support for the better comprehension of exacerbate and deleterious inflammatory response in the tuberculosis. (AU)

Scientific publications

(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)

PINEROS, A. R.; CAMPOS, L. W.; FONSECA, D. M.; BERTOLINI, T. B.; GEMBRE, A. F.; PRADO, R. Q.; ALVES-FILHO, J. C.; RAMOS, S. G.; RUSSO, M.; BONATO, V. L. D.. M2 macrophages or IL-33 treatment attenuate ongoing Mycobacterium tuberculosis infection. SCIENTIFIC REPORTS, v. 7, JAN 27 2017. (08/07861-3, 09/13689-1)