Autoregulation mechanism of human neutrophil apoptosis during bacterial infection.

Neutrophils (PMN), potent phagocytes, are the first line of the host immune defence against microorganisms, especially bacteria. Their half-life is very short and they are eliminated through apoptosis. Delayed neutrophil apoptosis is a characteristic feature of human osteomyelitis arising from Gram-negative or Gram-positive bacterial infection. The aim of this study was to investigate the modulation of apoptosis during infection of the human neutrophils by Staphylococcus aureus or Escherichia coli, the most common isolate in osteomyelitis. Analysis of host cells by flow cytometry using propidium iodide or annexin V labelling revealed an apoptosis inhibition after bacterial infection or treatment with LPS or LTA. We detected the secretion of cytokines such as IL-6, TNF-alpha and IL-1 beta by infected neutrophils. The addition of monoclonal antibodies to each cytokine abolished the protection against apoptosis. The anti-apoptotic Bcl-x(L) protein expression was increased and the pro-apoptotic Bax-alpha protein expression was decreased. These results identify a novel apoptotic effect in bacteria-infected cells that is mainly dependent on auto-production of cytokines and is correlated with Bax-alpha/Bcl-x(L) ratio. This may be a mechanism through which to resolve bacterial osteomyelitis infection.