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.
The interaction of host macrophage (Mphi) and Mycobacterium tuberculosis (Mtb) is mediated by cell surface receptors and is important in establishing intracellular infection. Mphis can kill invading organisms via reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). Using a Complement Receptor 3 (CR3) knockout mouse model we have examined whether the presence of CR3 affects the binding and uptake of viable Mtb by Mphis, the survival of the ingested bacteria and the induction of ROI and RNI during this interaction. We show that, although CR3 plays a role in the uptake of viable Mtb, the receptor plays no role in the subsequent survival of the bacteria. The finding holds true for resident Mphis and for interferon-gamma (IFN-gamma) activated Mphis, both in the absence and presence of serum opsonins. Activation of Mphi populations with IFN-gamma significantly inhibits the growth of Mtb in host Mphis and enhances the production of ROI and RNI. However, the presence of CR3 was not critical in any of these mechanisms. Furthermore, we demonstrate that the control of intracellular growth of Mtb in IFN-gamma activated Mphis is not mediated by a direct effect of RNI.
Rooyakkers
Amanda W J
AW
Department of Paediatrics, University of British Columbia, Vancouver, BC, Canada.
Stokes
Richard W
RW
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D013482:Superoxide Dismutase