Related Experiment Video
Updated: May 28, 2026
Isolation of Murine Peritoneal Macrophages to Carry Out Gene Expression Analysis Upon Toll-like Receptors Stimulation
Published on: April 29, 2015
Recruited macrophages control dissemination of group A Streptococcus from infected soft tissues
Inbal Mishalian1, Merav Ordan, Amnon Peled
1Department of Microbiology and Molecular Genetics, Faculty of Medicine, The Institute for Medical Research - Israel-Canada, The Hebrew University, Jerusalem 91120, Israel.
Abstract:
Group A Streptococcus (GAS) causes diverse infections in humans, ranging from mild to life-threatening invasive diseases, such as necrotizing fasciitis (NF), a rapidly progressing deep tissue infection. Despite prompt treatments, NF remains a significant cause of morbidity and mortality, even in previously healthy individuals. The early recruitment of leukocytes is crucial to the outcome of NF; however, although the role of polymorphonuclear neutrophils (PMNs) in host defense against NF is well established, the role of recruited macrophages remains poorly defined. Using a cutaneous murine model mimicking human NF, we found that mice deficient in TNF-α were highly susceptible to s.c. infections with GAS, and a paucity of macrophages, but not PMNs, was demonstrated. To test whether the effects of TNF-α on the outcome of infection are mediated by macrophages/monocytes, we systemically depleted C57BL/6 mice of monocytes by pharmacological and genetic approaches. Systemic monocyte depletion substantially increased bacterial dissemination from soft tissues without affecting the number of recruited PMNs or altering the bacterial loads in soft tissues. Enhanced GAS dissemination could be reverted by either i.v. injection of monocytes or s.c. administration of peritoneal macrophages. These experiments demonstrated that recruited macrophages play a key role in defense against the extracellular pathogen GAS by limiting its spread from soft tissues.
Insights
Group A Streptococcus (GAS) infections, like necrotizing fasciitis, are serious. Macrophages, not neutrophils, are key in limiting GAS spread from tissues, crucial for controlling this pathogen.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Group A Streptococcus (GAS) causes mild to severe human infections, including necrotizing fasciitis (NF).
- Early leukocyte recruitment is vital for NF outcomes, but macrophage roles are unclear despite established neutrophil functions.
- Tumor necrosis factor-alpha (TNF-α) influences susceptibility to GAS infections.
Purpose of the Study:
- To investigate the role of macrophages in host defense against Group A Streptococcus (GAS) during cutaneous infections.
- To determine if TNF-α's protective effects against GAS are mediated by macrophages/monocytes.
- To elucidate the contribution of macrophages to limiting bacterial spread in necrotizing fasciitis models.
Main Methods:
- Utilized a cutaneous murine model of GAS infection that mimics human necrotizing fasciitis.
- Employed pharmacological and genetic methods to systemically deplete monocytes in C57BL/6 mice.
- Assessed bacterial dissemination, recruited polymorphonuclear neutrophils (PMNs), and bacterial loads in soft tissues.
- Administered monocytes or macrophages intravenously or subcutaneously to evaluate rescue effects.
Main Results:
- Mice deficient in TNF-α exhibited increased susceptibility to GAS, with a notable lack of macrophages but not PMNs.
- Systemic monocyte depletion led to greater GAS dissemination from soft tissues without altering PMN recruitment or local bacterial loads.
- The enhanced GAS dissemination resulting from monocyte depletion was reversed by the administration of monocytes or macrophages.
- Recruited macrophages were shown to limit the spread of GAS from soft tissues.
Conclusions:
- Recruited macrophages play a critical role in host defense against the extracellular pathogen Group A Streptococcus.
- Macrophages are essential for limiting the dissemination of GAS from infection sites.
- These findings highlight macrophages as key players in combating invasive GAS infections, particularly necrotizing fasciitis.
Related Concept Videos
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:40Cell-mediated Immune Responses
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...