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

IFN-gamma -dependent hypersensitivity to LPS is inducible in mice by infect ion or pre-treatment with killed bacteria. Hypersensitive mice exhibit enha nced inflammatory responses to LPS, including the overproduction of TNF-alp ha. Using Lps(n) BALB/c and Lps(d) BALB/c/l mice, primed with Propionibacte rium acnes or infected with Salmonella typhimurium, we show that concurrent ly to hypersensitivity to LPS, a hypersensitivity to other constituents of killed Gram-negative or Grampositive bacteria and to staphylococcal enterot oxin B (SEB) develops. The TNF-alpha hyper-responses in sensitized mice ind uced by different Gram-positive bacteria, are generally weaker than those b y Gramnegative bacteria and vary significantly, due to the absence of a com mon, LPS-equivalent component. Using IEN-gammaR(-/-) and the respective wil d-type mice, we demonstrate that although sensitization to LPS and killed L isteria monocytogenes is exclusively IFN-gamma -dependent, an IFN-gamma -in dependent,, moderate sensitization to certain TNF-alpha -inducing constitue nts in bacteria may develop in parallel.