Mycobacterial infection: Immune evasion, host susceptibility and immunological markers of diagnostic importance
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology2008 (English)Doctoral thesis, monograph (Other academic)
IIn the first study, we investigated the functional implications of prolonged TLR signalling on IFN-γ mediated killing of mycobacteria by murine macrophages in vitro. TLR2, but not TLR4 ligation interfered with IFN-γ mediated killing of mycobacteria in macrophages. In terms of mechanisms, neither TNF nor nitric oxide (NO) production was significantly affected, and the refractoriness induced could be reversed with increasing amounts of IFN-γ In the second study, we aimed to identify immunological markers of diagnostic importance in both the respiratory tract and serum during pulmonary mycobacterial infection in mice. We found that increased levels of immunological markers in the respiratory tract, but not serum, correlated better with active mycobacterial infection in the lungs, suggesting that the immune response in the respiratory tract is more reflective of the infection status and pathology than the systemic response. Finally, we investigated the level and nature of immune responses to pulmonary mycobacterial infection in BALB/c and C57BL/6 mice, two mouse strains known to exhibit different susceptibilities to infection with several intracellular pathogens, including mycobacteria. We showed that increased susceptibility of BALB/c mice to early mycobacterial infection was associated with reduced Th1 immune responses, and increased sTNFR secretion in the lung. Moreover, BALB/c mice recruited fewer monocytes/macrophages to the lung, and although IFN-γ stimulation of infected bone marrow derived macrophages in both mouse strains resulted in induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The work presented in this thesis provide further insight into the mechanisms involved in the host-pathogen interaction; from persistence, to the immunological processes induced by the pathogen, to susceptibility of the host to infection.
Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2008. , 85 p.
Mycobacteria, Mice, Toll-like receptors, interferon gamma, immunological markers, lung, respiratory tract, susceptibility
Immunology in the medical area
Research subject Immunology
IdentifiersURN: urn:nbn:se:su:diva-8208ISBN: 978-91-7155-737-7OAI: oai:DiVA.org:su-8208DiVA: diva2:199807
2008-10-17, Ahlmansalen, Geovetenskapens hus, Svante Arrhenius väg 8, Stockholm, 10:00
Dieli, Francesco, Professor
Fernandez, Carmen, Professor
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