TNF-α hyper-responses to Gram-negative and Gram-positive bacteria in Propionibacterium acnes primed or Salmonella typhimurium infected mice

IFN-γ-dependent hypersensitivity to LPS is inducible in mice by infection or pre-treatment with killed bacteria. Hypersensitive mice exhibit enhanced inflammatory responses to LPS, including the overproduction of TNF-α. Using LpsnBALB/c and LpsdBALB/c/l mice, primed with Propionibacterium acnesor infected with Salmonella typhimurium, we show that concurrently to hypersensitivity to LPS, a hypersensitivity to other constituents of killed Gram-negative or Gram-positive bacteria and to staphylococcal enterotoxin B (SEB) develops. The TNF-α hyper-responses in sensitized mice induced by different Gram-positive bacteria, are generally weaker than those by Gram-negative bacteria and vary significantly, due to the absence of a common, LPS-equivalent component. Using IFN-γR—/—and the respective wild-type mice, we demonstrate that although sensitization to LPS and killed Listeria monocytogenesis exclusively IFN-γ-dependent, an IFN-γ-independent, moderate sensitization to certain TNF-α-inducing constituents in bacteria may develop in parallel.