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Mode of immunopotentiating action of BCG: macrophage activation produced by BCG-infection
Abstract:
Macrophage activation as measured by increased rate of carbon clearance and spreading of peritoneal macrophage was studied in mice infected with BCG, strain Japan. BCG caused marked increase of the numbers of peritoneal cells and spread macrophages. The increases of spread macrophages reached a peak at the 3rd week of BCG infection introduced by the both routes of intravenous(i.v.) injection and foot pad(f.p.) injection. BCG also enhanced the clearance of carbon. In the case of BCG given i.v., the increase of the rate of carbon clearance was biphasic : an early increase reaching maximum at the 1st week and a late increase reaching maximum at the 3rd week of BCG infection. When BCG given into one foot pad, peak increase was reached at the 5th week. The activation of macrophages as measured by increased levels of carbon clearance and increased numbers of spread macrophages in the mice receiving BCG i.v. was approximately two fold greater than that in the mice receiving BCG by f.p. route. When sheep red blood cells (SRBC) as antigen were injected i.v. into the mice primed with BCG i.v., the optimal interval between BCG priming and subsequent antigen injection varied with the dose of antigen for the induction of the highest level of delayed type hypersensitivity (DTH) to SRBC, but not with the degree of macrophage activation.
Insights
Bacillus Calmette-Guérin (BCG) infection in mice enhances macrophage activation, indicated by increased carbon clearance and macrophage spreading. Intravenous BCG administration resulted in a more pronounced activation compared to footpad injection.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophage activation is a critical component of the immune response.
- Bacillus Calmette-Guérin (BCG) is known to modulate immune cell activity.
Purpose of the Study:
- To investigate the effects of BCG infection on macrophage activation in mice.
- To compare the efficacy of different BCG administration routes (intravenous vs. footpad) on macrophage activation.
- To examine the relationship between BCG-induced macrophage activation and delayed-type hypersensitivity (DTH) response.
Main Methods:
- Mice were infected with BCG via intravenous (i.v.) or footpad (f.p.) injection.
- Macrophage activation was assessed by measuring carbon clearance rates and the percentage of spread peritoneal macrophages.
- Delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was evaluated after BCG priming.
Main Results:
- BCG infection significantly increased peritoneal cell numbers and spread macrophages, peaking at week 3 post-infection for both i.v. and f.p. routes.
- Carbon clearance was enhanced, showing a biphasic increase for i.v. BCG (peaks at weeks 1 and 3) and a single peak at week 5 for f.p. BCG.
- Intravenous BCG administration led to approximately double the macrophage activation compared to the footpad route; DTH response varied with antigen dose, not macrophage activation levels.
Conclusions:
- BCG infection effectively activates macrophages in mice, with intravenous administration yielding a stronger response.
- The degree of BCG-induced macrophage activation does not directly correlate with the optimal interval for subsequent DTH induction.
- These findings highlight the differential impact of BCG delivery routes on innate immune activation and adaptive immune priming.