THE PHOP LOCUS INFLUENCES PROCESSING AND PRESENTATION OF SALMONELLA-TYPHIMURIUM ANTIGENS BY ACTIVATED MACROPHAGES

The destruction and processing of bacteria by activated macrophages fa cilitates the presentation of antigens to T cells and thereby promotes the induction of specific immunity. The PhoP-PhoQ regulatory system t hat controls the synthesis of many Salmonella proteins required for vi rulence and survival within macrophages is one mechanism that this par ticular intracellular pathogen has evolved to resist destruction. To a ddress whether the phoP locus also influences antigen processing durin g the interaction of Salmonella typhimurium with macrophages, we teste d the effect of phoP mutations on the processing and presentation of m odel antigens expressed by the bacteria. Activated macrophages process ed phoP(-) bacteria with greater efficiency than wild-type bacteria, a s measured by the response of antigen-specific T-hybridoma cells; Salm onella constitutively expressing PhoP were processed even less efficie ntly than wild-type Salmonella. After heat-inactivation, however, both wild-type and phoP(-) bacteria were efficiently processed. The altere d processing and presentation efficiency was not due to differences in the level of antigen expressed by the bacteria or differences in the level of bacterial uptake by the macrophages. In addition, phoP-regula ted gene expression was shown to influence processing of antigen phago cytosed independently of the bacteria. Thus, phoP-regulated gene produ cts decrease the processing and presentation of S. typhimorium antigen s, demonstrating a role for this virulence locus in the inhibition of the induction of specific immunity.