Host responses to Plasmodium yoelii hepatic stages: A paradigm in host-parasite interaction

The liver stage of malaria, caused by the genus Plasmodium, is clinically s ilent, but immunologically significant. Ample evidence exists for an effect ive CD8(+) T cell response to this stage as well as the involvement of gamm a deltaT cells and NK1.1(int) cells in immunized animal models, In contrast , there is little information concerning responses in a naive host. Here we report that several host gene expressions in the liver, spleen, and kidney of BALB/c mice are altered during the liver stage of Plasmodium yoelii inf ection. Really interesting new gene 3 (Ring3), semaphorin subclass 4 member G, glutamylcysteine synthetase, and p45 NF erythroid 2 were all up-regulat ed 24 h after infection with P. yoelii. Semaphorin subclass 4 member G expr ession was elevated in the kidney, whereas Ring3 was elevated in both splee n and kidney. The expression of TNF-alpha (TNF-alpha and IFN-gamma) were do wn-regulated in all three tissues tested except in infected spleen where IF N-gamma was elevated, P. yoelii-related host gene changes were compared wit h those in Toxoplasma gondii-infected livers. Ring3 expression increased 5- fold over control values, whereas expression of the other transcripts remai ned unchanged. TNF-alpha and IFN-gamma expressions were increased in the To xoplasma-infected livers. The uniform increase of Ring3 expression in both Plasmodium- and Toxoplasma-infected livers suggests an innate immune respon se against parasitic infections, whereas the other gene expression changes are consistent with Plasmodium parasite-specific responses. Taken together, these changes suggest the immune responses to P. yoelii infection are both parasite and organ specific.