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Extracellular Superoxide Dismutase Enhances Recruitment of Immature Neutrophils to the Liver
Timothy J Break1, Alexandra R Witter1, Mohanalaxmi Indramohan1
1Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Abstract:
Listeria monocytogenes is a Gram-positive intracellular pathogen that causes spontaneous abortion in pregnant women, as well as septicemia, meningitis, and gastroenteritis, primarily in immunocompromised individuals. Although L. monocytogenes can usually be effectively treated with antibiotics, there is still around a 25% mortality rate with individuals who develop clinical listeriosis. Neutrophils are innate immune cells required for the clearance of pathogenic organisms, including L. monocytogenes The diverse roles of neutrophils during both infectious and noninfectious inflammation have recently gained much attention. However, the impact of reactive oxygen species, and the enzymes that control their production, on neutrophil recruitment and function is not well understood. Using congenic mice with varying levels of extracellular superoxide dismutase (ecSOD) activity, we have recently shown that the presence of ecSOD decreases clearance of L. monocytogenes while increasing the recruitment of neutrophils that are not protective in the liver. The data presented here show that ecSOD activity does not lead to a cell-intrinsic increase in neutrophil-homing potential or a decrease in protection against L. monocytogenes Instead, ecSOD activity enhances the production of neutrophil-attracting factors and protects hyaluronic acid (HA) from damage. Furthermore, neutrophils from the livers of ecSOD-expressing mice have decreased intracellular and surface-bound myeloperoxidase, are less capable of killing phagocytosed L. monocytogenes, and have decreased oxidative burst. Collectively, our data reveal that ecSOD activity modulates neutrophil recruitment and function in a cell-extrinsic fashion, highlighting the importance of the enzyme in protecting tissues from oxidative damage.
Insights
Extracellular superoxide dismutase (ecSOD) activity enhances neutrophil recruitment but impairs their function in fighting Listeria monocytogenes infection. This suggests ecSOD protects tissues from damage by modulating immune cell responses.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Listeria monocytogenes is a dangerous pathogen causing severe illness and death, especially in vulnerable populations.
- Neutrophils are key immune cells for fighting infections, but their precise role in Listeria monocytogenes infections is complex.
- The influence of reactive oxygen species and enzymes like extracellular superoxide dismutase (ecSOD) on neutrophil function during infection is not fully understood.
Purpose of the Study:
- To investigate the impact of extracellular superoxide dismutase (ecSOD) activity on neutrophil recruitment and function during Listeria monocytogenes infection.
- To clarify whether ecSOD affects neutrophil behavior intrinsically or through external factors.
Main Methods:
- Utilized congenic mice with varying levels of ecSOD activity to study Listeria monocytogenes infection.
- Analyzed neutrophil recruitment, function, and killing capacity in the context of different ecSOD levels.
- Assessed the production of neutrophil-attracting factors and the integrity of hyaluronic acid (HA).
Main Results:
- ecSOD activity enhances the production of factors that attract neutrophils to the infection site.
- ecSOD protects hyaluronic acid (HA) from degradation, potentially influencing the inflammatory environment.
- Neutrophils in ecSOD-expressing mice showed reduced myeloperoxidase activity and impaired killing of Listeria monocytogenes.
- Neutrophil oxidative burst capacity was diminished in the presence of ecSOD.
Conclusions:
- ecSOD modulates neutrophil recruitment and function in a manner that is external to the neutrophils themselves.
- While ecSOD may enhance neutrophil numbers at the site of infection, it compromises their effectiveness in clearing Listeria monocytogenes.
- The findings highlight ecSOD's crucial role in protecting tissues from oxidative damage during bacterial infections by influencing immune cell responses.
