Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus.
We found that mice infected with different isolates of lymphocytic choriomeningitis virus (LCMV) develop a mild hemorrhagic anemia, which becomes severe and eventually lethal in animals depleted of platelets or lacking integrin beta3. Lethal hemorrhagic anemia is mediated by virus-induced IFN-alpha/beta that causes platelet dysfunction, mucocutaneous blood loss and suppression of erythropoiesis. In addition to the life-threatening hemorrhagic anemia, platelet-depleted mice fail to mount an efficient cytotoxic T lymphocyte (CTL) response and cannot clear LCMV. Transfusion of functional platelets into these animals reduces hemorrhage, prevents death and restores CTL-induced viral clearance in a manner partially dependent on CD40 ligand (CD40L). These results indicate that, upon activation, platelets expressing integrin beta3 and CD40L are required for protecting the host against the induction of an IFN-alpha/beta-dependent lethal hemorrhagic diathesis and for clearing LCMV infection through CTLs.
Iannacone
Matteo
M
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Sitia
Giovanni
G
Isogawa
Masanori
M
Whitmire
Jason K
JK
Marchese
Patrizia
P
Chisari
Francis V
FV
Ruggeri
Zaverio M
ZM
Guidotti
Luca G
LG
D000818:Animals; D001792:Blood Platelets / Q000821:virology*; D001803:Blood Transfusion; D003602:Cytotoxicity, Immunologic; D006470:Hemorrhage / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism* / Q000821:virology*; D013921:Thrombocytopenia / Q000821:virology
D039661:Integrin beta3; D016898:Interferon-alpha; D016899:Interferon-beta