GENES FOR CHEMOKINES MUMIG AND CRG-2 INDUCED IN PROTOZOAN AND VIRAL-INFECTIONS IN RESPONSE TO IFN-GAMMA WITH PATTERNS OF TISSUE EXPRESSION THAT SUGGEST NONREDUNDANT ROLES IN-VIVO

MuMig and Crg-2 are IFN-inducible murine chemokines whose human homolo gues, MuMig and IP-10, respectively, share activity in vitro as T cell chemoattractants. We analyzed the expression of the genes Mumig, crg- 2, and IFN-gamma during experimental infections with Plasmodium yoelii , Toxoplasma gondii, and vaccinia virus. Mumig, crg-2 and IFN-gamma we re induced in multiple organs. During the acute phase of each infectio n as well as after i.p. injection of rIFN-gamma, levels of Mumig mRNA in the liver were as high or higher than levels in any of the other or gans. In contrast, the organs showing the highest expression of crg-2 and IFN-gamma varied among the experimental models, with induction of these latter two genes colocalizing. Differences in relative levels of expression of Mumig and crg-2 in liver and spleen were not demonstrab ly due to expression of the genes in different cell types within these organs. We showed that both Mumig and crg-2 are induced in the liver in hepatocytes and in the spleen in CD11b(+) cells. IFN-gamma was nece ssary for induction of Mumig during infections with T. gondii or vacci nia virus. In contrast, induction of crg-2 was not completely dependen t on IFN-gamma. These data demonstrate that despite the overlap in act ivities within chemokine subsets, chemokine genes show differences in their patterns of expression and in their responses to inducers that s uggest nonredundant roles in vivo. Moreover, the pattern of induction of crg-2 is consistent with Crg-2 acting primarily locally, while the pattern for Mumig induction suggests that Mumig induction suggests tha t MuMig may have a systemic role during infection.