Spirochete-platelet attachment and thrombocytopenia in murine relapsing fever borreliosis.
Thrombocytopenia is common in persons infected with relapsing fever Borreliae. We previously showed that the relapsing fever spirochete Borrelia hermsii binds to and activates human platelets in vitro and that, after platelet activation, high-level spirochete-platelet attachment is mediated by integrin alpha IIb beta 3, a receptor that requires platelet activation for full function. Here we established that B hermsii infection of the mouse results in severe thrombocytopenia and a functional defect in hemostasis caused by accelerated platelet loss. Disseminated intravascular coagulation, immune thrombocytopenic purpura, or splenic sequestration did not play a discernible role in this model. Instead, spirochete-platelet complexes were detected in the blood of infected mice, suggesting that platelet attachment by bacteria might result in platelet clearance. Consistent with this, splenomegaly and thrombocytopenia temporally correlated with spirochetemia, and the severity of thrombocytopenia directly correlated with the degree of spirochetemia. Activation of platelets and integrin alpha IIb beta 3 were apparently not required for bacterium-platelet binding or platelet clearance because the bacterium-bound platelets in the circulation were not activated, and platelet binding and thrombocytopenia during infection of beta 3-deficient and wild-type mice were indistinguishable. These findings suggest that thrombocytopenia of relapsing fever is the result of platelet clearance after beta 3-independent bacterial attachment to circulating platelets.
Alugupalli
Kishore R
KR
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave N, Worcester, MA 01655, USA.
Michelson
Alan D
AD
Joris
Isabelle
I
Schwan
Tom G
TG
Hodivala-Dilke
Kairbaan
K
Hynes
Richard O
RO
Leong
John M
JM
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism* / Q000382:microbiology; D001854:Bone Marrow Cells / Q000378:metabolism; D001899:Borrelia Infections / Q000097:blood*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D012061:Relapsing Fever; D013144:Spirochaetales / Q000378:metabolism*; D013921:Thrombocytopenia / Q000097:blood*; D013997:Time Factors
D019039:Platelet Glycoprotein GPIIb-IIIa Complex