Study of activation of the CD40 pathway and interaction with Candida albicans infection in an orthotopic HPV associated mouse model

• Grant number: 11/23860-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2012
• Effective date (End): June 30, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Paula Lepique
• Grantee: Aleida Maria da Silva Lima
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Tumors associated with infection by human papillomavirus are a public health problem in developing countries. Despite the prophylactic vaccine commercially available, the study of mechanisms trigger tolerance by the tumor are very important for new immunotherapies. Our laboratory has been using a tumor model associated with HPV16, strain TC-1 injected subcutaneously in mice, which allowed us to the time characterize important processes started by tumor cells that induce tolerance in the system host immune. We have demonstrated, for example, the myeloid infiltration and the expression of IL-10 by the same, are essential to induce regulatory phenotype in T lymphocytes and inhibits anti-tumor response. We also demonstrated that B lymphocytes participate in modulation of the response of T lymphocytes, and it can be reversed when the CD40 pathway is activated in B cells Our proposal now is to generate and characterize a new model study of HPV-associated lesions, but in vaginal epithelium of mice, in association or not with infection with Candida albicans, a fungus that commonly infects the lower female genital tract. In this model, tumor cells are instilled in the vagina mice, tumor growth and immune responses to tumor will be monitored over time. Currently several research groups have suggested, supported by data such as number of lymphocytes and concentration of immunoglobulins, the presence of a diffuse lymphoid organ associated with female genital organ. Beneath this perspective we believe that the characterization of responses to tumors using orthotopic models are of great importance. Moreover, the study of responses immunity in hosts who have lesions associated with HPV and other infections will also be a contribution extremely relevant to the area.