Abstract
This study shows that in mice selectively depleted of neutrophils by treatment with a monoclonal antibody, RB6-8C5, listeriosis is severely exacerbated in the liver, but not in the spleen or peritoneal cavity during the crucial first day of infection. At sites of infection in the livers of neutrophil-depleted mice, Listeria monocytogenes grew to large numbers inside hepatocytes. By contrast, in the livers of normal mice neutrophils rapidly accumulated at infectious foci and this was associated with the lysis of infected hepatocytes that served to abort infection in these permissive cells. In the spleen the situation was different, in that depletion of neutrophils did not result in appreciable exacerbation of infection. In this organ intact infected cells, many of which appeared to be fibroblast-like stromal cells, were found at foci of infection in the presence or absence of large numbers of neutrophils. This suggests that neutrophils are less effective at destroying L. monocytogenes-infected target cells in the spleen than in the liver. Consequently, at least during the first day, the organism remained free to multiply intracellularly in the spleen in cells that are permissive for its growth. Presumably, the same situation exists in the peritoneal cavity, because depleting neutrophils did not severely exacerbate infection initiated at this site.
Highlights
Specificity and Depleting Capacity of mAb RB6-8C5. It has been reported by others [15] that mAb RB6-8C5 binds to and selectively depletes mature murine neutrophils and eosinophils
The published study does not present detailed cytofluorimetric data in support of this interpretation. It was recently reported by another group [17] that RB6-8C5 can bind to a significant proportion of CD8 § and CD4 + T cells from naive mice and from mice infected with L. monocytogenes
Given this latter claim it was necessary to reexamine the specificity of RB6-8C5 for neutrophils and eosinophils before conducting any in vivo experiments with it
Summary
Male CB6/F1 mice were obtained from the Trudean Institute Animal Breeding Facility. They were used when they were 9-12 wk old. Monocytogenes (strain EDG) was prepared as described previously [13] and stored frozen at - 7 0 ~ in 1-ml aliquots. For each experiment vials of frozen bacteria were thawed, pelleted by centrifugation (16,000 g for 5 rain), resuspended, and diluted in sterile 0.9% (wt/vol) saline to the required inoculum concentration
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