Related Experiment Videos
Microbicidal activities of Salmonella typhimurium- and interferon-gamma-activated mouse peritoneal macrophages
J A Langermans1, P H Nibbering, M E van der Hulst
1Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Abstract:
Activation of mouse peritoneal macrophages during infection of mice by various facultative intracellular bacteria and after intravenous injection of recombinant interferon-gamma (rIFN-gamma) was studied. Macrophage activation was demonstrated on the basis of three different criteria, i.e. inhibition of Toxoplasma gondii proliferation, enhanced release of H2O2 and increased expression of Ia antigen. Macrophages activated during an infection with Salmonella typhimurium showed no enhanced salmonellacidal or listericidal activity relative to control macrophages, whereas Listeria-activated macrophages killed Listeria but not Salmonella faster than control macrophages. The rate of proliferation of Salmonella in spleen and liver of activated mice was comparable to the proliferation in the organs of control mice. rIFN-gamma-activated macrophages displayed neither an enhanced salmonellacidal nor an enhanced listericidal activity. When high numbers of Listeria were injected intravenously the proliferation in spleen and liver of rIFN-gamma-treated and control mice was similar. The proliferation of Listeria in the liver of rIFN-gamma-treated mice was less than in control mice when 1 LD50 or lower numbers of bacteria were injected. It is concluded that peritoneal macrophages become activated during infections of mice with various intracellular pathogens. However, these activated macrophages do not show enhanced bactericidal activity against all bacteria. Furthermore, rIFN-gamma is not sufficient to enhance the listericidal activity of macrophages.
Insights
Infection activates mouse macrophages, but this does not guarantee enhanced bacterial killing. Recombinant interferon-gamma (rIFN-gamma) alone is insufficient to boost macrophage listericidal activity.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Peritoneal macrophages play a crucial role in the innate immune response against intracellular pathogens.
- Macrophage activation is a complex process that can be triggered by various stimuli, including microbial infections and cytokines like interferon-gamma.
- Assessing macrophage activation requires multiple functional criteria, such as pathogen growth inhibition, reactive oxygen species production, and antigen expression.
Purpose of the Study:
- To investigate the activation status of mouse peritoneal macrophages during infections with facultative intracellular bacteria.
- To evaluate the impact of recombinant interferon-gamma (rIFN-gamma) on macrophage activation and bactericidal activity.
- To determine if activated macrophages exhibit enhanced killing of specific bacterial pathogens like Salmonella and Listeria.
Main Methods:
- Infection of mice with Salmonella typhimurium and Listeria monocytogenes.
- Intravenous injection of recombinant interferon-gamma (rIFN-gamma) into mice.
- Assessment of macrophage activation using criteria: inhibition of Toxoplasma gondii proliferation, enhanced hydrogen peroxide (H2O2) release, and increased Ia antigen expression.
- Quantification of bacterial proliferation rates in spleen and liver tissues.
- Evaluation of bactericidal activity against Salmonella and Listeria.
Main Results:
- Macrophages activated during Salmonella typhimurium infection did not show enhanced killing of Salmonella or Listeria.
- Listeria-activated macrophages exhibited increased killing of Listeria but not Salmonella.
- Recombinant interferon-gamma (rIFN-gamma) administration did not enhance macrophage killing of Salmonella or Listeria.
- Bacterial proliferation rates in spleen and liver were comparable between activated and control mice for Salmonella.
- Listeria proliferation was reduced in the liver of rIFN-gamma-treated mice only when low bacterial doses (≤1 LD50) were administered.
Conclusions:
- Peritoneal macrophages become activated during infections with intracellular pathogens.
- Macrophage activation does not confer enhanced bactericidal activity against all bacterial species.
- Recombinant interferon-gamma (rIFN-gamma) alone is not sufficient to enhance the listericidal activity of macrophages in vivo.