TY - JOUR
T1 - Extracellular superoxide dismutase enhances recruitment of immature neutrophils to the liver
AU - Break, Timothy J.
AU - Witter, Alexandra R.
AU - Indramohan, Mohanalaxmi
AU - Mummert, Mark E.
AU - Dory, Ladislav
AU - Berg, Rance E.
N1 - Funding Information:
We thank Herenia Armenta, Mariano Aufiero, and Jessica M. F. Hall for technical assistance. Flow cytometry was performed in the Flow Cytometry and Laser Capture Microdissection Core Facility at the University of North Texas Health Science Center. This work was supported by a grant from NIH/NIAID (AI109630) to R.E.B., a BioLegend grant to R.E.B. and T.J.B., Intramural seed grants from UNTHSC to R.E.B. and T.J.B., a Sigma Xi Grant-In-Aid of Research grant to T.J.B., and an AAI Careers in Immunology fellowship to R.E.B. and A.R.W.
Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85002813595&partnerID=8YFLogxK
U2 - 10.1128/IAI.00603-16
DO - 10.1128/IAI.00603-16
M3 - Article
C2 - 27600509
AN - SCOPUS:85002813595
SN - 0019-9567
VL - 84
SP - 3302
EP - 3312
JO - Infection and Immunity
JF - Infection and Immunity
IS - 12
ER -