scholarly journals Genetic Control of the Innate Immune Response to Borrelia hermsii Influences the Course of Relapsing Fever in Inbred Strains of Mice

2009 ◽  
Vol 78 (2) ◽  
pp. 586-594 ◽  
Author(s):  
Vivian M. Benoit ◽  
Annett Petrich ◽  
Kishore R. Alugupalli ◽  
Robin Marty-Roix ◽  
Annette Moter ◽  
...  

ABSTRACT 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.

2000 ◽  
Vol 68 (7) ◽  
pp. 3900-3908 ◽  
Author(s):  
Brian Stevenson ◽  
Stephen F. Porcella ◽  
Katrina L. Oie ◽  
Cecily A. Fitzpatrick ◽  
Sandra J. Raffel ◽  
...  

ABSTRACT Borrelia hermsii, an agent of tick-borne relapsing fever, was found to contain multiple circular plasmids approximately 30 kb in size. Sequencing of a DNA library constructed from circular plasmid fragments enabled assembly of a composite DNA sequence that is homologous to the cp32 plasmid family of the Lyme disease spirochete,B. burgdorferi. Analysis of another relapsing fever bacterium, B. parkeri, indicated that it contains linear homologs of the B. hermsii and B. burgdorfericp32 plasmids. The B. hermsii cp32 plasmids encode homologs of the B. burgdorferi Mlp and Bdr antigenic proteins and BlyA/BlyB putative hemolysins, but homologs of B. burgdorferi erp genes were absent. Immunoblot analyses demonstrated that relapsing fever patients produced antibodies to Mlp proteins, indicating that those proteins are synthesized by the spirochetes during human infection. Conservation of cp32-encoded genes in differentBorrelia species suggests that their protein products serve functions essential to both relapsing fever and Lyme disease spirochetes. Relapsing fever borreliae replicate to high levels in the blood of infected animals, permitting direct detection and possible functional studies of Mlp, Bdr, BlyA/BlyB, and other cp32-encoded proteins in vivo.


1974 ◽  
Vol 139 (2) ◽  
pp. 313-322 ◽  
Author(s):  
Pablo Rubinstein ◽  
Ngukoy Liu ◽  
Edwin W. Streun ◽  
Francine Decary

A quantitative method has been developed to determine agglutinability of mouse red blood cells. Tests with different inbred strains of mice revealed only two phenotypes. The same inbred strains were tested with the cytopherometer to determine the electrophoretic mobility of the corresponding red cells. Again, two phenotypes were uncovered, and faster mobility was found in the red cells that had higher agglutinability. The genetic control of this character is autosomal and codominant, and segregates independently of H-2 and coat color.


1978 ◽  
Vol 147 (1) ◽  
pp. 39-49 ◽  
Author(s):  
J Watson ◽  
M Largen ◽  
K P McAdam

A number of altered immunologic responses to lipopolysaccharide (LPS) in C3H/HeJ mice result from the expression in B lymphocytes of a defective genetic locus, termed Lps. Lps has been mapped to chromosome 4 between two loci, Mup-1 and Ps. As it is difficult to type individual mice for LPS responsiveness in more than one type of assay, we have utilized Mup-1 as a genetic marker to correlate LPS responses in mice to the expression of the Lps locus. Three nonlymphoid responses to LPS have been examined in 12 recombinant inbred strains of mice and in a backcross linkage analysis, and are all regulated by the expression of the Lps locus. These responses are hypothermal changes in body temperature, and the elevation in serum levels of a colony stimulating factor and the precursor of the secondary amyloid protein AA. Therefore, the initiation of LPS responses in different cell types in mice involve the expression of a common locus. These linkage studies provide a means for analyzing the genetic control of many of the diverse reactions of the endotoxic response to LPS.


2005 ◽  
Vol 73 (5) ◽  
pp. 3025-3037 ◽  
Author(s):  
Cyril Guyard ◽  
Earl M. Chester ◽  
Sandra J. Raffel ◽  
Merry E. Schrumpf ◽  
Paul F. Policastro ◽  
...  

ABSTRACT Genome sequencing of the relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae identified three open reading frames (ORFs) on the chromosomes that contained internal, tandemly repeated amino acid sequences that were absent in the Lyme disease spirochete Borrelia burgdorferi. The predicted amino acid sequences of these genes (BH0209, BH0512, and BH0553) have hydrophobic N termini, indicating that these proteins may be secreted. B. hermsii transcribed the three ORFs in vitro, and the BH0512- and BH0553-encoded proteins (PBH-512 and PBH-553) were produced in vitro and in experimentally infected mice. PBH-512 and PBH-553 were on the spirochete's outer surface, and antiserum to these proteins reduced the adherence of B. hermsii to red blood cells. PCR analyses of 28 isolates of B. hermsii and 8 isolates of B. turicatae demonstrated polymorphism in each gene correlated with the number of repeats. Serum samples from relapsing fever patients reacted with recombinant PBH-512 and PBH-553, suggesting that these proteins are produced during human infection. These polymorphic proteins may be involved in the pathogenicity of these relapsing fever spirochetes and provide a mechanism for antigenic heterogeneity within their populations.


1982 ◽  
Vol 24 (3) ◽  
pp. 343-346 ◽  
Author(s):  
D. R. Pollard ◽  
B. Woodward ◽  
Kamlesh Gupta

Normal levels of circulating serum alpha-fetoprotein (AFP) in different inbred strains of mice, as determined by radioimmunoassay, are reported. These strains show different and characteristic values for the mean serum AFP concentration, suggesting genetic control of the serum level of this protein. Furthermore, within each strain a difference in serum levels of the protein is observed between sexes; males have a significantly higher serum AFP concentration.


1981 ◽  
Vol 23 (1) ◽  
pp. 155-157 ◽  
Author(s):  
Stan R. Blecher ◽  
Bala Bhaskar Gollapudi ◽  
Om P. Kamra

Highly inbred strains of mice have contrasting means and low ranges for the trait of gonosomal univalency at diakinesis-metaphase I. Randomly bred and mixed strains have wider ranges. The inbred strain DBA/2J has a high mean, and this character is evidently transmitted through the male parent. This material may provide a valuable model for study of genetic control of XY pairing.


Parasitology ◽  
1975 ◽  
Vol 71 (1) ◽  
pp. 51-60 ◽  
Author(s):  
P. Wakelin

A comparison has been made of the responses of random-bred CFLP and inbred NIH mice to infection with Trichuris muris. Random-bred mice showed greater variation in worm burdens and less uniformity in worm expulsion. Irradiation prior to infection reduced variation, but did not increase the mean level of infection above that shown by the most susceptible unirradiated mice. In NIH mice, however, irradiation raised the level of infection in all mice. The factors responsible for variation between CFLP mice and for the level of infection in NIH mice came into play after the fifth day of infection and were inactivated by cortisone acetate. It is suggested that these factors are immunologically mediated and under direct genetic control. Uniformity of infection and expulsion in NIH mice is therefore seen as a consequence of genetic uniformity; variability in CFLP mice as a consequence of genetic variation.The time of worm expulsion was found to differ markedly between inbred strains of mice. Hybrid progeny showed the expulsion time characteristic of the parental strain with the most rapid expulsion; greater resistance was therefore inherited as a dominant characteristic. The genetic control of immunity to T. muris is discussed in the context of the antibody- and cell-mediated components of the expulsion process.


Sign in / Sign up

Export Citation Format

Share Document