CXC chemokine ligand 10 controls viral infection in the central nervous system: evidence for a role in innate immune response through recruitment and activation of natural killer cells.
How chemokines shape the immune response to viral infection of the central nervous system (CNS) has largely been considered within the context of recruitment and activation of antigen-specific lymphocytes. However, chemokines are expressed early following viral infection, suggesting an important role in coordinating innate immune responses. Herein, we evaluated the contributions of CXC chemokine ligand 10 (CXCL10) in promoting innate defense mechanisms following coronavirus infection of the CNS. Intracerebral infection of RAG1(-/-) mice with a recombinant CXCL10-expressing murine coronavirus (mouse hepatitis virus) resulted in protection from disease and increased survival that correlated with a significant increase in recruitment and activation of natural killer (NK) cells within the CNS. Accumulation of NK cells resulted in a reduction in viral titers that was dependent on gamma interferon secretion. These results indicate that CXCL10 expression plays a pivotal role in defense following coronavirus infection of the CNS by enhancing innate immune responses.
Trifilo
Matthew J
MJ
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA.
Montalto-Morrison
Cynthia
C
Stiles
Linda N
LN
Hurst
Kelley R
KR
Hardison
Jenny L
JL
Manning
Jerry E
JE
Masters
Paul S
PS
Lane
Thomas E
TE
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000821:virology*; D002460:Cell Line; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000821:virology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D018352:Coronavirus Infections / Q000276:immunology / Q000821:virology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000235:genetics / Q000472:pathogenicity*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007371:Interferon-gamma