Full text
| |
| Author(s): |
Elyara Maria Soares
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2013-09-13 |
| Examining board members: |
Lucia Helena Faccioli;
Maria da Gloria Bonecini Almeida;
Cleni Mara Marzocchi Machado;
Alexandra Ivo de Medeiros;
Moisés Palaci
|
| Advisor: | Lucia Helena Faccioli |
| Abstract | |
The mechanisms that confer resistance to Mycobacterium tuberculosis (Mtb) for destruction by the host, in addition to its ability to retain and/or multiply within phagocytic cells are still poorly understood. Our research group has contributed to the understanding of the role of lipid mediators, including prostaglandins (PGs) and leukotrienes (LTs) in tuberculosis. PGs inhibit Th1 cell immune response, cytokine production and phagocytosis, thus facilitating the infection. LTs are involved in the leukocytes recruitment, and modulation of cytokine synthesis, phagocytosis and microbicidal mechanisms enhancement, and contribute to the elimination of the mycobacteria. In this project, we evaluated in vivo and in vitro the lipid mediators production induced by Mtb strains isolated from patients with active tuberculosis. We demonstrated in this study that alveolar macrophages infected with bacilli from SV009 strain lead to an increase of TNF- production and nitrite, than those infected with the strain SV068. In contrast, alveolar macrophages infected with bacilli from SV068 strain induced more LTB4 production when compared to SV009 infection. We obtained higher recovery colony forming units (CFU) of alveolar macrophages treated with MK886 and infected with bacilli from SV068 strain; while more CFUs were recovered after treatment with caffeic acid and infection with bacilli from SV009 strain. Regarding the lipid bodies (LBs) formation, we observed a greater number of these structures, when alveolar macrophages were infected with bacilli from SV068 strain. Still, we observed a decrease of LBs when the macrophages were treated with MK886 and caffeic acid. Bacilli from SV068 strain were more phagocytosed, but macrophages were not very effective in the microbicidal activity. In the in vivo experiments we found that mice infected with SV068 strain die more than the other and MK886 treatment partially protects the mice, besides, the mortality is not related to the higher bacterial load in the lung or spleen. There was an increase in neutrophil recruitment induced after infection, especially after infection with SV068 strain, and treatment with MK886 significantly inhibits recruitment when compared to infection with SV009 strain. Mononuclear cells were also recruited and remained increased until the end of the observed period, without many significant differences when comparing infection with SV009 and SV068 strains. The nitrite production was also found greater in animals infected with bacilli from SV068 strain. Histopathological analysis of the infected mice lungs showed an intense inflammatory reaction with greater impairment of the mice lungs when infected with bacilli from SV068 strain with an intense collagen deposition and multiplication of bacilli. We suggest that the SV068 strain is more virulent and participates of the immune response by lipid mediators dependent mechanisms. (AU) | |
| FAPESP's process: | 09/01689-7 - Evaluation of Participation of Lipids Mediators in the Experimental Infections Induced by Diferents Human Isolates of Mycobacterium tuberculosis |
| Grantee: | Elyara Maria Soares |
| Support Opportunities: | Scholarships in Brazil - Doctorate |