title: Innate immune response to encephalomyocarditis virus infection mediated by CD1d.
abstract: CD1d-reactive natural killer T (NKT) cells can rapidly produce T helper type 1 (Th1) and/or Th2 cytokines, can activate antigen-presenting cell (APC) interleukin-12 (IL-12) production, and are implicated in the regulation of adaptive immune responses. The role of the CD1d system was assessed during infection with encephalomyocarditis virus (EMCV-D), a picornavirus that causes acute diabetes, paralysis and myocarditis. EMCV-D resistance depends on IL-12-mediated interferon-gamma (IFN-gamma) production. CD1d-deficient mice, which also lack CD1d-reactive NKT cells, were substantially more sensitive to infection with EMCV-D. Infected CD1d knockout mice had decreased IL-12 levels in vitro and in vivo, and indeed were protected by treatment with exogenous IL-12. IFN-gamma production in CD1d knockout mice was decreased compared with that in wild-type (WT) mice in response to EMCV-D in vitro, although differences were not detected in vivo. Treatment with anti-asialo-GM1 antibody, to deplete NK cells, caused a marked increase in susceptibility of WT mice to EMCV-D infection, whereas CD1d knockout mice were little affected, suggesting that NK-cell-mediated protection is CD1d-dependent. Therefore, these data indicate that CD1d is essential for optimal responses to acute picornaviral infection. We propose that CD1d-reactive T cells respond to early immune signals and function in the innate immune response to a physiological viral infection by rapidly augmenting APC IL-12 production and activating NK cells.
authors: Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. mexley@caregroup.harvard.edu
authors: Mark A
authors: MA
authors: Exley
authors: Nancy J
authors: NJ
authors: Bigley
authors: Olivia
authors: O
authors: Cheng
authors: Angela
authors: A
authors: Shaulov
authors: Syed Muhammad Ali
authors: SM
authors: Tahir
authors: Quincy L
authors: QL
authors: Carter
authors: Jorge
authors: J
authors: Garcia
authors: Carren
authors: C
authors: Wang
authors: Kurt
authors: K
authors: Patten
authors: Harold F
authors: HF
authors: Stills
authors: Frederick W
authors: FW
authors: Alt
authors: Scott B
authors: SB
authors: Snapper
authors: Steven P
authors: SP
authors: Balk
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D015139:Blotting, Southern / Q000379:methods; D018188:Cardiovirus Infections / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D004686:Encephalomyocarditis virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005951:Glucose Tolerance Test / Q000379:methods; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D018664:Interleukin-12; D007371:Interferon-gamma