Failure to induce IFN-β production during Staphylococcus aureus infection contributes to pathogenicity.

The importance of type I IFNs in the host response to viral infection is well established; however, their role in bacterial infection is not fully understood. Several bacteria (both Gram-positive and -negative) have been shown to induce IFN-beta production in myeloid cells, but this IFN-beta is not always beneficial to the host. We examined whether Staphylococcus aureus induces IFN-beta from myeloid phagocytes, and if so, whether it is helpful or harmful to the host to do so. We found that S. aureus poorly induces IFN-beta production compared with other bacteria. S. aureus is highly resistant to degradation in the phagosome because it is resistant to lysozyme. Using a mutant that is more sensitive to lysozyme, we show that phagosomal degradation and release of intracellular ligands is essential for induction of IFN-beta and inflammatory chemokines downstream of IFN-beta. Further, we found that adding exogenous IFN-beta during S. aureus infection (in vitro and in vivo) was protective. Together, the data demonstrate that failure to induce IFN-beta production during S. aureus infection contributes to pathogenicity. The Journal of Immunology, 2012, 189: 4537-4545.