Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin

Area of Science:

• Immunology
• Microbiology
• Pathophysiology

Background:

• Mycobacterium bovis (BCG) infection confers extreme sensitivity to bacterial lipopolysaccharides (LPS) in mice.
• BCG infection activates macrophages, a cell type implicated in LPS-induced pathophysiological effects.
• Understanding the in vitro macrophage response to LPS post-BCG infection is crucial for elucidating in vivo lethality.

Purpose of the Study:

• To investigate whether macrophages from BCG-infected mice exhibit increased susceptibility to lipopolysaccharides (LPS) in vitro.
• To correlate in vitro macrophage sensitivity to LPS with the observed in vivo lethal effects of LPS in BCG-infected mice.

Main Methods:

• C57BL/6 mice (LPS-susceptible) and C3H/HeJ mice (LPS-resistant) were infected intravenously with Mycobacterium bovis (BCG).
• The 50% lethal dose (LD50) of LPS was determined in BCG-infected and control mice.
• Peritoneal macrophages were isolated from BCG-infected and control mice to assess their susceptibility to LPS in vitro.
• Acquired cellular resistance was evaluated by assessing the ability of macrophages to inhibit Listeria monocytogenes growth.

Main Results:

• BCG infection in C57BL/6 mice led to a significant reduction in LPS LD50, starting at 7 days and persisting for weeks.
• Macrophages from BCG-infected C57BL/6 mice demonstrated markedly increased susceptibility to LPS in vitro.
• This increased macrophage susceptibility correlated with the development of acquired cellular resistance.
• BCG infection did not alter LPS LD50 or macrophage sensitivity in LPS-resistant C3H/HeJ mice.

Conclusions:

• The heightened susceptibility of BCG-infected mice to lethal LPS effects is mirrored by increased in vitro macrophage sensitivity.
• The release of vasoactive substances from activated, LPS-susceptible macrophages in vivo likely contributes to the observed lethality.
• Macrophage activation state is a critical determinant of host response to lipopolysaccharides following BCG infection.