Figure 1.
B. duttonii spirochetemia in mice.
BALB/c (A), NUDE (B), SCID (C), and SCID BEIGE (D) mice. B. duttonii established infection in all four mouse strains. Spirochetemia was significantly (p = 0.02) higher in B-cell-deficient mice (C, D). No differences were observed between wild-type and T-cell-deficient mice (A vs. B) or between SCID mice and NK-cell-deficient SCID BEIGE mice (C vs. D). Data are presented as medians with 25th and 75th percentiles. Notice that the scales of the y-axes in this figure differ from those in Figures 2 and 4.
Figure 2.
B. recurrentis spirochetemia in SCID BEIGE and SCID mice.
B. recurrentis established a relatively low-grade (compared to B. duttonii, see Figure 1C, D), stable infection in SCID BEIGE and SCID mice, but not in BALB/c or NUDE animals. Strain A17 (panel A) caused a higher (p<0.01) level of spirochetemia than did strain A11 (panel B). No difference in B. recurrentis spirochetemia was observed between SCID BEIGE and SCID mice. Data are presented as medians with 25th and 75th percentiles.
Figure 3.
Splenomegaly in infected mice.
Although expansion of B- and T-cells is the major cause of splenomegaly in wild-type animals, SCID BEIGE mice infected with B. recurrentis A17 displayed significant (p<0.01) splenomegaly,which indicates a T-, B-, and NK-cell-independent immune response.
Figure 4.
Effect of clodronate-induced macrophage depletion on spirochetemia.
Mice were injected with clodronate liposomes in PBS to deplete macrophages (and other phagocytic cells) in the blood and in organs in contact with the blood (e.g., the spleen and liver). PBS was used as a negative control. The injections (indicated by black triangles) were given every fifth day, starting one day before infection. A. BALB/c mice infected with B. duttonii developed very high spirochetemia, and all except one individual (dotted line) died at day 6 p.i. B. B. duttonii-infected SCID BEIGE mice treated with clodronate developed uncontrolled spirochetemia, and they all died before day 8 p.i. Control SCID BEIGE and BALB/c mice injected with PBS had much lower spirochetemia compared to their macrophage-depleted counterparts. C. SCID BEIGE mice treated with clodronate and infected with B. recurrentis A17 developed high but not lethal spirochetemia. The maximum spirochetemia in any of the control SCID BEIGE and BALB/c mice injected with PBS was 7.3×106/ml. Even between the two peaks shown for the B. recurrentis-infected, clodronate-treated mice, the median spirochetemia was never below 8×106/ml. B. recurrentis was unable to establish detectable spirochetemia in macrophage-depleted BALB/c mice.