Susceptibility Differences to Cryptosporidium parvum Infection in Two Strains of Gamma Interferon Knockout Mice

Abstract

Differences in susceptibility to cryptosporidial infections were investigated between 2 strains of gamma interferon knockout (GKO) mice. Male C57BL/6J-Ifg and BALB/c-Ifg (GKO) mice, ages 8-10 wk, were inoculated with infectious oocysts at various doses. C57BL/6J-Ifg mice developed overwhelming infections and died 9-12 days after infection. Low inoculum doses (1 x 10(3)) did not increase the survival time significantly. The infection intensity in C57BL/6J-Ifg mice inoculated with 1 x 10(5) oocysts/mouse increased markedly on day 4 postinfection (PI) and continued to increase significantly over the next 6-7 days. Most of the C57BL/6J-Ifg mice exceeded 15% weight loss and died by day 10 PI. In contrast, BALB/c-Ifg mice developed moderate infections from which they recovered. The average parasite load in the BALB/c-Ifg mice was 100 times lower than in C57BL/6J-Ifg mice. Mice survived until termination of the experiment (39 days) even when 1 x 10(6) oocysts per mouse were used for inoculation. BALB/c-Ifg mice did not exhibit significant weight loss (or difference in stool consistency). These 2 mouse strains make excellent models for studying differences in recovering and nonrecovering immune mechanisms.

Intestinal Immune Response to HumanCryptosporidiumsp. Infection

“…In murine models, IFN-␥ is a critical mediator of the innate and acquired immune responses controlling cryptosporidiosis (10,52,66,87). Similarly, severe Cryptosporidium-associated diarrhea has been described for HIV-negative individuals with IFN-␥ deficiency (28).…”

CD4+T Cells Are Not Essential for Control of Early AcuteCryptosporidium parvumInfection in Neonatal Mice

“…Studies suggest that in adaptive immunity to C. parvum, IFN-␥ and IL-12 also have protective roles in adult mice, indicating the involvement of Th1 responses (5,24). Ultimate control of infection in adult mice and humans is dependent on CD4 ϩ T cells (2,27), and IFN-␥ expression by these cells could be a key factor in host defense, although in humans, this cytokine might be more important during secondary infection (12,14,36).…”

Cryptosporidium parvum-Specific Mucosal Immune Response in C57BL/6 Neonatal and Gamma Interferon-Deficient Mice: Role of Tumor Necrosis Factor Alpha in Protection

“…Some possibilities, not mutually exclusive, include a direct toxic effect of IFN-␥ on the parasite or the infected cells or the induction of other cytokines that can be toxic for the parasite or of chemoattractants for immune cells. Mead and You reported that susceptible BALB/c-GKO mice recover from infection whereas C57BL/6-GKO mice remain chronically infected (24), suggesting that other immune components related to the genetic background of the mice play a role in the susceptibility of mice to C. parvum infection.…”