Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly important for clearance in the liver, but the ability of PMN from susceptible and resistant mice to directly kill L. monocytogenes has not been examined. In this study, we showed that PMN infiltrated the livers of BALB/c/By/J (BALB/c) and C57BL/6 (B6) mice in similar numbers and that both cell types readily migrated toward leukotriene B4 in an in vitro chemotaxis assay. However, CFU burdens in the liver were significantly higher in BALB/c mice than in other strains, suggesting that PMN in the BALB/c liver might not be able to clear L. monocytogenes as efficiently as B6 PMN. Unprimed PMN harvested from either BALB/c or B6 bone marrow killed L. monocytogenes directly ex vivo, and pretreatment with autologous serum significantly enhanced killing efficiency for both. L. monocytogenes were internalized within 10 min and rapidly triggered intracellular production of reactive oxygen species in a dose-dependent manner. However, PMN from gp91phox-deficient mice also readily killed L. monocytogenes, which suggested that nonoxidative killing mechanisms may be sufficient for bacterial clearance. Together, these results indicate that there is not an intrinsic defect in the ability of PMN from susceptible BALB/c mice to kill L. monocytogenes and further suggest that if PMN function is impaired in BALB/c mice, it is likely due to locally produced modulating factors present in the liver during infection.
|Journal||Infection and Immunity|
|State||Published - Apr 1 2018|
Bibliographical noteFunding Information:
We thank Carole Parent and Ritankar Majumdar for helpful discussions regarding the under-agarose assay. We also thank Jennifer Strange and Greg Bauman in the University of Kentucky Flow Cytometry Core and Thomas Wilkop in the University of Kentucky Light Microscopy Core for their technical assistance. This work was supported by Public Health Service grant AI101373 to S.E.F.D.
©2018 American Society for Microbiology.
- BALB/cBy/J mice
- C57BL/6 mice
- Innate immunity
- Reactive oxygen species
ASJC Scopus subject areas
- Infectious Diseases