Differentiation between virulent and avirulent strains of Rickettsia prowazekii by macrophage-like cell lines

The growth of avirulent (E) and virulent (Breinl) strains of Rickettsia prowazekii was compared in four mouse macrophage-like cell lines (RAW264.7, J774.1, P388D1, and PU5), one human macrophage-like cell line (U937-1), and the mouse fibroblast line L929. The E and Breinl strains grew equally well in L929 cells. However, all of the mouse macrophage-like cell lines clearly differentiated between the two strains by restricting the growth of the E strain relative to that of the Breinl strain. A nonuniform response to infection was sometimes observed in which E strain rickettsiae were cleared from the majority of the infected cells, but multiplied in some of the remaining infected cells. The human line U937-1 was not very effective at differentiating the E and Breinl strains. Addition of rabbit antirickettsial antiserum to the Breinl or E strains of R. prowazekii immediately before infection of L929 cells caused a marked decrease in the initial infection but had no effect on the subsequent growth of the rickettsiae in the L929 cells. In contrast, addition of antiserum to Breinl or E strain rickettsiae immediately before infection of macrophage-like cell lines caused either no change or an increase in the initial infection. Most of the rickettsiae that infected the mouse macrophage-like cell lines in the presence of antiserum were destroyed in these cell lines. Thus, when the infection took place in the presence of antiserum, the mouse macrophage-like cell lines no longer differentiated between the E and Breinl strains. These data indicate that mouse macrophage-like cell lines should be a useful model system for defining the differences between the E and Breinl strains of Rickettsia prowazekii, differences which should lead to an understanding of the biochemical basis of virulence in this organism.