Measles virus infection induces chemokine synthesis by neurons.
The role that neurons play in the induction of the immune response following CNS viral infection is poorly understood, largely owing to the belief that these cells are immunologically quiescent. In this report, we show that virus infection of neurons results in the synthesis of proinflammatory chemokines, which are early and important mediators of leukocyte recruitment to sites of viral infection. For these studies, a transgenic mouse model of neuron-restricted measles virus (MV) infection was used. Inoculation of immunocompetent and immunodeficient transgenic adult mice resulted in CNS induction of the mRNAs encoding IFN-gamma inducible protein of 10 kD, monokine inducible by gamma and RANTES. Colocalization of chemokine proteins with MV-infected neurons was detected by immunofluorescence in infected brain sections. Both IFN-gamma inducible protein 10 kD and RANTES were also induced in MV-infected primary hippocampal neurons cultured from transgenic embryos, as shown by RNase protection assay, confocal microscopy, and ELISA. Interestingly, neuronal infection with another RNA virus (lymphocytic choriomeningitis virus) was not associated with induction of these chemokines. In immunocompetent mice, chemokine synthesis preceded the infiltration of T lymphocytes, and chemokine ablation by neutralizing Abs resulted in a 20-50% reduction in the number of infiltrating lymphocytes. Collectively, these data indicate that neurons play an important role in the recruitment of a protective antiviral response to the CNS following viral infection, although such a role may be virus type-dependent.
Patterson
Catherine E
CE
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Daley
John K
JK
Echols
Lisa A
LA
Lane
Thomas E
TE
Rall
Glenn F
GF
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D020805:Central Nervous System Viral Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008459:Measles virus / Q000276:immunology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000473:pathology
D015703:Antigens, CD; D018946:Chemokine CCL5; D018925:Chemokines; D007106:Immune Sera; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010751:Phosphopyruvate Hydratase