SALMONELLA INFECTIONS IN THE ABSENCE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX-II

We examined the pathogenesis of the facultative intracellular bacteriu m, Salmonella typhimurium iu MHCII-/-, C2D knock-out mice, and wild-ty pe C57BL/6J mice, The MHCII knock-out shortened the kinetics of animal death lid reduced the dose of S. typhimurium needed to kill mice, We measured the physiological and cytokine responses of both mouse strain s after S. typhimurium injection, Animal weight loss, spleen weights, liver weights, thymus weights, and serum corticosterone concentrations were comparable after injection with several doses of bacteria, The o nly physiological differences observed between the two strains were ob served 3 days after injection of the, highest dose of bacteria tested, Serum concentrations of tumor necrosis factor alpha, interleukin-2, a nd interleukin-6 increased in a dose-dependent fashion irrespective of mouse MHCII expression, Therefore, even in the absence of MHCII, mice are able to mount relatively normal physiological and immunological r esponses, Consistent with these normal responses, an increased percent age of MHCII-/- mice, primed with a low dose of bacteria 13 days earli er, were able to survive a lethal challenge of Salmonella compared wit h unprimed controls, Lastly, C2D mice had significantly higher serum i nterleukin-10 concentrations than C57BL/6J mice 48 h after infection w ith all doses of S. typhimurium, C2D macrophages also secreted signifi cantly more IL-10 and less NO and O-2(-) after lipopolysaccharide or p horbol ester stimulation in vitro than wild-type macrophages.