Genes for chemokines MuMig and Crg-2 are 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 homologues, HuMig 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 were induced in multiple organs. During the acute phase of each infection 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 organs. 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 demonstrably 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 necessary for induction of Mumig during infections with T. gondii or vaccinia virus. In contrast, induction of crg-2 was not completely dependent on IFN-gamma. These data demonstrate that despite the overlap in activities within chemokine subsets, chemokine genes show differences in their patterns of expression and in their responses to inducers that suggest 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 may have a systemic role during infection.
Amichay
D
D
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Gazzinelli
R T
RT
Karupiah
G
G
Moench
T R
TR
Sher
A
A
Farber
J M
JM
D000818:Animals; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D019743:Chemokines, CXC; D005786:Gene Expression Regulation / Q000276:immunology*; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009928:Organ Specificity / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology*; D014615:Vaccinia / Q000235:genetics / Q000276:immunology*
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D015846:Monokines; D007371:Interferon-gamma