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Absence of complement receptor 3 results in reduced binding and ingestion of Mycobacterium tuberculosis but has no significant effect on the induction of reactive oxygen and nitrogen intermediates or on the survival of the bacteria in resident and interferon-gamma activated macrophages

University of British Columbia

The interaction of host macrophage (MΦ) and Mycobacterium tuberculosis (Mtb) is mediated by cell surface receptors and is important in establishing intracellular infection. MΦs are part of the mammalian defenses against microbial infection and can kill invading organisms via reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). Using a Complement Receptor 3 (CR3) knockout mouse model I have examined whether the presence of CR3 affected the binding and uptake of Mtb by resident and activated MΦ, the survival of the ingested bacteria and the induction of ROI and RNI during this interaction. I have shown that, although CR3 plays a definitive role in the uptake of Mtb, the receptor played no role in the subsequent survival of the bacteria. The finding held true for resident MΦs in the absence and presence of serum opsonins and also in Interferon-gamma (IFN-γ) activated MΦs. Activation of MΦpopulations with IFN- γ significantly inhibited the growth of Mtb in host MΦs and enhanced the respiratory burst and production of nitric oxide (NO). However, the presence of CR3 was not found to be critical in any of these mechanisms. Furthermore, I demonstrated that the control of intracellular growth of Mtb in IFN- γ activated MΦs was not mediated by a direct effect of NO.

Thesis/Dissertation

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2009-11-24

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http://hdl.handle.net/2429/15708

Experimental Medicine

University of British Columbia

UBCV

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