Acquired resistance to facultative intracellular parasites was investigated in C57BL/6J inbred mice susceptibe to Salmonella typhimurium but inherently resistant to Listeria monocytogenes and in A/J inbred mice which showed the reverse relationship. A/J but not C57BL/6J mice were protected against S. typhimurium challenge by S. typhimurium phenol vaccine, S. typhimurium purified RNA, or L. monocytogenes purified RNA. C57BL/6J but not A/J could be protected against L. monocytogenes challenge by L. monocytogenes phenol vaccine, S. typhimurium RNA, or L. monocytogenes RNA. Yeast RNA, calf thymus RNA, BCG and poly (I:C) protected A/J against Salmonella and C57BL/6J against Listeria challenge. Enumeration of viable organisms in the RNA and BCG-stimulated animals after challenge indicated that macrophage activation had probably taken place. The RNA-elicited protection was long lasting and waned after about 60 days. Enhanced resistance to S. typhimurium and L. monocytogenes can be stimulated by nonliving substances bearing no known antigenic relationship to the pathogen. Enhanced resistance is elicited only in the host with a background of inherent resistance to the specific pathogen.
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