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Mycobacterial infection: Immune evasion, host susceptibility and immunological markers of diagnostic importance
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
Responsible organisation
2008 (English)Doctoral thesis, monograph (Other academic)
Abstract [en]

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.
Keyword [en]
Mycobacteria, Mice, Toll-like receptors, interferon gamma, immunological markers, lung, respiratory tract, susceptibility
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-8208ISBN: 978-91-7155-737-7 (print)OAI: oai:DiVA.org:su-8208DiVA: diva2:199807
Public defence
2008-10-17, Ahlmansalen, Geovetenskapens hus, Svante Arrhenius väg 8, Stockholm, 10:00
Opponent
Supervisors
Available from: 2008-09-25 Created: 2008-09-25Bibliographically approved
List of papers
1. TLR2 but not TLR4 signalling is critically involved in the inhibition of IFN-γ induced killing of mycobacteria by murine macrophages.
Open this publication in new window or tab >>TLR2 but not TLR4 signalling is critically involved in the inhibition of IFN-γ induced killing of mycobacteria by murine macrophages.
2007 In: Scandinavian journal of immunology, ISSN 0300-9475, Vol. 65, no 2, 148-157 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25475 (URN)
Note
Part of urn:nbn:se:su:diva-8208Available from: 2008-09-25 Created: 2008-09-25Bibliographically approved
2.
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3. Early immune responses are responsible for the better control of pulmonary mycobacterial infection in C57BL/6 compared with BALB/c mice.
Open this publication in new window or tab >>Early immune responses are responsible for the better control of pulmonary mycobacterial infection in C57BL/6 compared with BALB/c mice.
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-25477 (URN)
Note
Part of urn:nbn:se:su:diva-8208Available from: 2008-09-25 Created: 2008-09-25 Last updated: 2010-01-13Bibliographically approved

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