INDUCTION OF HEPATIC INFLAMMATORY RESPONSE BY PLASMODIUM-BERGHEI-SPOROZOITES PROTECTS BALB-C MICE AGAINST CHALLENGE WITH PLASMODIUM-YOELII SPOROZOITES

BALB/c mice are about 2,000 times less susceptible to sporozoites of P lasmodium berghei than to Plasmodium yoelii. Associated with this is t he innate cellular response mounted after injection with P. berghei. H ost inflammatory cells do not normally attack P. yoelii during their d evelopment as exoerythrocytic forms (EEFs) in the liver. We used P. be rghei sporozoites to induce host inflammation that might act against d eveloping P.yoelii EEFs. Mice injected with P. herghei sporozoites fol lowed 1 hr later with P. yoelii had a 58% reduction in P. yoelii EEFs. To establish whether this was due to events that occurred before vs. after invasion of hepatocytes by P. yoelii sporozoites, mice received P. yoelii sporozoites that were allowed to invade for 1 hr before subs equent injection with P. berghei; these mice showed minimal reduction in P. yoelii EEFs. Thus, most of the deleterious effects of P. berghei sporozoites appear to have been directed against P. yoelii sporozoite s prior to their invasion of hepatocytes. Plasmodium yoelii that had a lready invaded were relatively unaffected. Further timing experiments showed that this effect was induced only by viable P. berghei sporozoi tes, which may thus induce rapid changes in sinusoid physiology leadin g to host resistance against P. yoelii sporozoites.