Genetic control of the innate immune response to Borrelia hermsii influences the course of relapsing fever in inbred strains of mice.
Host susceptibility to infection is controlled in large measure by the genetic makeup of the host. Spirochetes of the genus Borrelia include nearly 40 species of vector-borne spirochetes that are capable of infecting a wide range of mammalian hosts, causing Lyme disease and relapsing fever. Relapsing fever is associated with high-level bacteremia, as well as hematologic manifestations, such as thrombocytopenia (i.e., low platelet numbers) and anemia. To facilitate studies of genetic control of susceptibility to Borrelia hermsii infection, we performed a systematic analysis of the course of infection using immunocompetent and immunocompromised inbred strains of mice. Our analysis revealed that sensitivity to B. hermsii infections is genetically controlled. In addition, whereas the role of adaptive immunity to relapsing fever-causing spirochetes is well documented, we found that innate immunity contributes significantly to the reduction of bacterial burden. Similar to human infection, the progression of the disease in mice was associated with thrombocytopenia and anemia. Histological and fluorescence in situ hybridization (FISH) analysis of infected tissues indicated that red blood cells (RBCs) were removed by tissue-resident macrophages, a process that could lead to anemia. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream by tissue phagocytes.
Benoit
Vivian M
VM
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Petrich
Annett
A
Alugupalli
Kishore R
KR
Marty-Roix
Robin
R
Moter
Annette
A
Leong
John M
JM
Boyartchuk
Victor L
VL
D000740:Anemia / Q000235:genetics / Q000382:microbiology; D000818:Animals; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012061:Relapsing Fever / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D012737:Sex Factors; D013921:Thrombocytopenia / Q000235:genetics / Q000382:microbiology