Reduced lymphocyte infiltration during cytomegalovirus brain infection of interleukin-10-deficient mice.
Interleukin (IL)-10 deficiency results in highly elevated levels of interferon (IFN)-gamma, as well as the IFN-gamma-inducible chemokines CXCL9 and CXCL10 within murine cytomegalovirus (MCMV)-infected brains. To test the hypothesis that these elevated chemokine levels would result in enhanced brain infiltration, we compared immune cell infiltration in response to MCMV brain infection between wild-type and IL-10 knockout (KO) mice. Longitudinal analysis following adoptive transfer of cells from beta-actin-luciferase transgenic wild-type mice showed maximal brain infiltration by peripheral immune cells occurred at 5 days post infection. Although the overall percentage of CD45(hi) cells infiltrating the brain was not altered by IL-10 deficiency, paradoxically, despite elevated chemokine levels, reduced T lymphocyte (CD8+) and natural killer (NK) (CD49b+) cell infiltration into the brain was observed in IL-10-deficient animals. This decreased lymphocyte infiltration was associated with elevated levels of the lymph node homing receptor L-selectin/CD62L on CD8+ T cells. Lymph node cells obtained from MCMV-infected mice deficient in IL-10 also displayed reduced migration towards CXCL10 when compared to wild-type animals. Taken together, these data show that despite elevated chemokine levels, absence of IL-10 results in reduced lymphocyte infiltration into MCMV-infected brains.
Cheeran
Maxim C-J
MC
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Mutnal
Manohar B
MB
Hu
Shuxian
S
Armien
Anibal
A
Lokensgard
James R
JR
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D054357:Chemokine CXCL10; D004660:Encephalitis / Q000276:immunology* / Q000821:virology; D005260:Female; D016753:Interleukin-10 / Q000172:deficiency*; D007694:Killer Cells, Natural / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D008156:Luciferases; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology*; D013154:Spleen / Q000166:cytology
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019041:L-Selectin; D016753:Interleukin-10; D008156:Luciferases