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Increased local complement levels upon intraperitoneal injection of mice with Listeria monocytogenes and regulation
Abstract:
Alternative complement pathway activity in mouse peritoneal fluid was determined by a sensitive microtiter assay with rabbit erythrocytes as target cells and cobra venom factor as the inducer of bystander hemolysis. The intra- and interstrain variations in five mouse strains were 30% and, maximally, 64%, respectively. No activity was detected in genetically C5-deficient mice. In C5-sufficient mice, intraperitoneal injection of heat-inactivated Listeria monocytogenes resulted in a 250% increase in local complement activity within 30 min. This effect was reversed by simultaneous injection of dextran sulfate but not heparin. These results are discussed in relation to the ability of listeriae to activate the mouse alternative complement pathway in vitro and the effectiveness of dextran sulfate and the failure of heparin in functioning as an adjuvant in the induction of a protective response in mice by a heat-inactivated listeria vaccine.
Insights
Mouse complement activity varies significantly between strains. Heat-inactivated Listeria monocytogenes boosts local complement, an effect modulated by dextran sulfate, not heparin, impacting vaccine adjuvant potential.
Area of Science:
- Immunology
- Microbiology
- Complement System Research
Background:
- The alternative complement pathway plays a crucial role in innate immunity.
- Understanding complement activation by pathogens like Listeria monocytogenes is vital for vaccine development.
- Variability in complement activity can influence immune responses and vaccine efficacy.
Purpose of the Study:
- To quantify alternative complement pathway activity in mouse peritoneal fluid.
- To investigate the impact of Listeria monocytogenes on local complement activity.
- To evaluate the adjuvant potential of dextran sulfate and heparin in a heat-inactivated Listeria vaccine model.
Main Methods:
- A microtiter assay using rabbit erythrocytes and cobra venom factor was employed to measure complement activity.
- Complement activity was assessed in five different mouse strains.
- The effect of intraperitoneal injection of heat-inactivated Listeria monocytogenes, with or without dextran sulfate or heparin, was evaluated.
Main Results:
- Significant intra- and interstrain variations in alternative complement pathway activity were observed (up to 64%).
- No complement activity was detected in C5-deficient mice, confirming the role of the complement system.
- Heat-inactivated Listeria monocytogenes induced a 250% increase in local complement activity within 30 minutes, which was reversed by dextran sulfate but not heparin.
Conclusions:
- Mouse alternative complement pathway activity exhibits considerable strain-dependent variation.
- Listeria monocytogenes effectively activates the alternative complement pathway in vivo.
- Dextran sulfate, but not heparin, acts as an adjuvant by modulating complement activity, suggesting its potential utility in vaccine formulations.