Effect of mouse lymphokines and cloned mouse interferon-gamma on the interaction of Rickettsia prowazekii with mouse macrophage-like RAW264.7 cells

We studied the effects of crude mouse lymphokines and cloned mouse interferon-gamma on the interaction of Rickettsia prowazekii with mouse macrophage-like RAW264.7 cells. Treatment of RAW264.7 cells with lymphokines before infection, after infection, or both before and after infection with R. prowazekii led to killing of a substantial proportion of the RAW264.7 cells. Such cytotoxicity required both lymphokines and viable R. prowazekii and did not occur in mouse fibroblastic L929 cells. Untreated cultures of RAW264.7 cells supported good growth of the Breinl strain of R. prowazekii, but in lymphokine-treated cultures, little or no rickettsial growth occurred in the cells that survived the cytotoxic reaction. In addition, treatment of RAW264.7 cells with lymphokines before rickettsial infection was associated with suppression of the initial infection. The effects of cloned mouse interferon-gamma were similar to the effects of crude mouse lymphokines. Assessment of cytotoxicity, inhibition of the initial infection, and inhibition of rickettsial growth in RAW264.7 cells pretreated with various concentrations of interferon-gamma indicated that the effects of the lymphokines could be explained by the interferon-gamma that was present in these preparations. Treatment of RAW264.7 cells with interferon-gamma makes them unsuitable host cells for R. prowazekii.