Innate resistance to Babesia infection is influenced by genetic background and gender

Abstract

Infection of severe combined immunodeficient mice with Babesia sp. strain WA1 was studied to assess the contributions of innate and adaptive immunity in resistance to acute babesiosis. The scid mutation showed little effect in genetically susceptible C3H mice and did not decrease the inherent resistance of C57BL/6 mice to the infection, suggesting that innate immunity plays a central role in determining the course of Babesia infection in these strains. In contrast, the scid mutation dramatically impaired resistance in moderately susceptible BALB/c mice, suggesting that acquired immunity may play an important secondary role. In comparison to their female counterparts, male mice of different genetic backgrounds showed increased resistance to the infection, indicating that the gender of the host may influence protection against babesiosis.

FIG. 1

Infection course in male mice carrying the scid mutation on the C57BL/6 and C3H genetic backgrounds. Closed squares, B6 (n = 23); open squares, B6 SCID (n = 17); closed circles, C3H (n = 20); open circles, C3H SCID (n = 18). (A) Survival was significantly lower in C3H and C3H SCID mice than in B6 and B6 SCID mice (P = 0.0001). The scid mutation did not cause a significant difference in survival in the B6 background (P = 0.2448). In the C3H background, SCID mice survived longer than controls (P = 0.0156). (B) Parasitemia levels were significantly elevated in C3H and C3H SCID mice compared to those of B6 and B6 SCID mice (P = 0.0003). No statistical difference due to the scid mutation was found in either genetic background. Mean parasitemia levels throughout infection were 7.78 (range, 4.63 to 11.76) in C3H SCID mice and 0.34 (range, 0.02 to 1.10) in B6 mice.

FIG. 2

Infection course in BALB/c male mice carrying the scid mutation. Closed squares, B6 (n = 23); open squares, B6 SCID (n = 17); closed triangles, BALB/c control; (n = 8); open triangles, BALB/c SCID (n = 9). (A) The scid mutation caused a significant decrease in survival in BALB/c mice compared to controls (P = 0.0007) and compared to SCID mice with the B6 genetic background (P = 0.0001). (B) Parasitemia levels were significantly elevated in BALB/c SCID mice compared to BALB/c controls and B6 SCID mice (P < 0.0001). Mean parasitemia levels were 9.35 (range, 6.36 to 12.91) for BALB/c SCID mice and 0.93 (range, 0.21 to 2.15) for BALB/c mice.

FIG. 3

Effect of gender on survival of mice of moderately susceptible strains after infection with Babesia sp. strain WA1. Open squares, Male; closed circles, female. Survival was significantly higher in males than in females (for AKR mice, P = 0.106; (B6 × 129)F1, P = 0.0204; 129/J, P = 0.06338; (C3B6 × C3H)F1, P = 0.0005).

FIG. 4

Gender influence on the infection course in C57BL/6 SCID mice. Open squares, B6 SCID males (n = 17); closed circles, B6 SCID females (n = 24). (A) Survival was significantly higher in males than in females (P = 0.0026). (B) Parasitemia levels were significantly higher in females than in males (P = 0.0004). Mean parasitemia levels were 0.34 (range, 0.02 to 0.10) for males and 3.84 (range, 2.27 to 5.82) for females.