Role of neutrophils in experimental septicemia and septic arthritis induced by Staphylococcus aureus

M Verdrengh, A Tarkowski - Infection and immunity, 1997 - Am Soc Microbiol
M Verdrengh, A Tarkowski
Infection and immunity, 1997Am Soc Microbiol
We have previously described a murine model of hematogenously induced Staphylococcus
aureus sepsis and arthritis. In this model, large numbers of granulocytes can be observed
both in the circulation and locally in the inflamed synovium within 24 h after bacterial
inoculation. To assess the role of neutrophils in this severe infection, mice were given
granulocyte-depleting monoclonal antibody RB6-8C5 before being inoculated with S.
aureus. All the control mice survived their intravenous injection with 3 x 10 (7) CFU of S …
We have previously described a murine model of hematogenously induced Staphylococcus aureus sepsis and arthritis. In this model, large numbers of granulocytes can be observed both in the circulation and locally in the inflamed synovium within 24 h after bacterial inoculation. To assess the role of neutrophils in this severe infection, mice were given granulocyte-depleting monoclonal antibody RB6-8C5 before being inoculated with S. aureus. All the control mice survived their intravenous injection with 3 x 10(7) CFU of S. aureus, whereas all the mice given RB6-8C5 antibody died of sepsis within 2 to 3 days. Even when the inoculum size was reduced sixfold (i.e., 6 x 10(6) CFU/mouse), 50% of the RB6-8C5-treated animals died within 6 days. The RB6-8C5-treated mice had a significantly higher burden of bacteria in their blood and kidneys 24 and 48 h after bacterial inoculation. In addition, when a suboptimal dose of bacteria was administered, the neutrophil-depleted animals displayed a higher frequency of arthritis than did the controls. The granulocyte-depleted animals exhibited increased levels of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-6, and gamma interferon, reflecting the severity of their disease. This is the first direct demonstration of neutrophils playing a crucial protective role in the early phase of S. aureus infection.
American Society for Microbiology