Plasma membrane expression of heat shock protein 60 in vivo in response toinfection

Heat shock protein 60 (hsp60) is constitutively expressed in the mitochondr ia of eukaryotic cells. However, it has been identified in other subcellula r compartments in several disease states and in transformed cells, and it i s an immunogenic molecule in various infectious and autoimmune diseases. To better understand the factors that influence expression of hsp60 in normal cells in vivo, we analyzed its cellular and subcellular distribution in mi ce infected with the intracellular bacterium Listeria monocytogenes. Wester n blotting of subcellular fractionated spleen cells showed that although en dogenous hsp60 was restricted to the mitochondria in noninfected animals, i t was associated with the plasma membrane as a result of infection. The low levels of plasma membrane-associated hsp60 seen in the livers in noninfect ed animals subsequently increased during infection. Plasma membrane hsp60 e xpression did not correlate with bacterial growth, being most evident durin g or after bacterial clearance and persisting at 3 weeks postinfection. Usi ng flow cytometry, we determined that Mac-1(+), T-cell receptor gamma delta (+) and B220(+) cells represented the major Hsp60(+) populations in spleens of infected mice. By contrast, B220(+) cells were the predominant hsp60(+) population in livers of infected mice. Of the immune cells analyzed, the k inetic profile of the gamma delta T-cell response most closely matched that of hsp60 expression in both the spleen and liver. Collectively, these find ings show that during infection hsp60 can be localized to the plasma membra ne of viable cells, particularly antigen-presenting cells, providing a mean s by which hsp60-reactive lymphocytes seen in various infectious disease an d autoimmune disorders may be generated and maintained.