Plasmodium chabaudi chabaudi: Effect of Low Parasitemias on Immunity in CB6F1 Mice (original) (raw)
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Infection and Immunity, 2006
Important to malaria vaccine design is the phenomenon of "strain-specific" immunity. Using an accurate and sensitive assay of parasite genotype, real-time quantitative PCR, we have investigated protective immunity against mixed infections of genetically distinct cloned "strains" of the rodent malaria parasite Plasmodium chabaudi chabaudi in mice. Four strains of P. c. chabaudi, AS, AJ, AQ, and CB, were studied. One round of blood infection and drug cure with a single strain resulted in a partial reduction in parasitemia, compared with levels for naïve mice, in challenge infections with mixed inocula of the immunizing (homologous) strain and a heterologous strain. In all cases, the numbers of blood-stage parasites of each genotype were reduced to similar degrees. After a second, homologous round of infection and drug cure followed by challenge with homologous and heterologous strains, the parasitemias were reduced even further. In these circumstances, moreover, the homologous strain was reduced much faster than the heterologous strain in all of the combinations tested. That the immunity induced by a single infection did not show "strain specificity," while the immunity following a second, homologous infection did, suggests that the "strain-specific" component of protective immunity in malaria may be dependent upon immune memory. The results show that strong, protective immunity induced by and effective against malaria parasites from a single parasite species has a significant "strain-specific" component and that this immunity operates differentially against genetically distinct parasites within the same infection.
Plasticity of Immune Responses Suppressing Parasitemia During AcutePlasmodium chabaudiMalaria
The Journal of Immunology
γδ T cells have a crucial role in cell-mediated immunity (CMI) against P. chabaudi malaria, but δ-chain knockout (KO) (δo/o) mice and mice depleted of γδ T cells with mAb cure this infection. To address the question of why mice deficient in γδ T cells resolve P. chabaudi infections, we immunized δo/o mice by infection with viable blood-stage parasites. Sera from infection-immunized mice were tested for their ability to protect JHo/o, δo/o double KO mice passively against P. chabaudi challenge infection. The onset of parasitemia was significantly delayed in mice receiving immune sera, compared with saline or uninfected serum controls. Immune sera were then fractionated into Ig-rich and Ig-depleted fractions by HPLC on a protein G column. Double KO mice were passively immunized with either fraction and challenged with P. chabaudi. The onset of parasitemia was significantly delayed in recipients of the Ig-rich fraction compared with recipients of the Ig-poor fraction of immune sera. We...
1996
C57BL/6 mice which were treated with recombinant mouse interleukin-6 (rmIL-6), 75 ng in 0.2 ml saline, i.p., 24 h before inoculation with Plasmodium chabaudi chabaudi and on days one, two and three could not control the primary acute parasitaemia but were able to suppress secondary parasitaemia significantly, peak of 3% and to reduce parasitaemia to subpatent levels within three weeks. Control C57BL/6 mice, which received saline injections only, developed two identical peaks of parasitaemia of at least 21% each, typical of a primary P. chabaudi chabaudi infection and cleared parasitaemia by day 28 post-inoculation. Serum levels of IL-6 measured in the first week by enzyme-linked immunosorbent assay were significantly higher (two-fold) in recipients compared to control mice. Anti-plasmodial IgG1, 2a and 2b titres were four to 16 times higher in rmIL-6 recipients than in the control mice. Reduction of parasitaemia to subpatency during the secondary phase of P. chabaudi chabaudi infection in C57BL/6 mice is primarily antibody-mediated and rmIL-6 accelerates this process by boosting the levels of the required specific anti-plasmodial IgG subclasses of antibodies.
Experimental Parasitology, 2004
Susceptible A/J and more resistant C57BL/6J mice were infected with Plasmodium chabaudi chabaudi 54X, P.c. chabaudi AS and Plasmodium chabaudi adami 408XZ. As expected, most C57BL/6J mice survived the infections with the different isolates. But in contrast to previous observations, not all A/J mice succumbed to infection: just over 50% of A/J mice survived infections with P.c. chabaudi 54X, while 80% survived P.c. chabaudi AS. The more virulent parasite, P.c. adami 408XZ, was able to kill all A/J mice and 20% of C57BL/6J mice after an intravenous infection with 10 5 pRBC. A detailed study of four parameters of pathology (body weight, body temperature, blood glucose and RBC counts) in both mouse strains after a P.c. adami 408XZ infection showed similar patterns to those previously reported after infection with P.c. chabaudi AS. These data suggest that environmental factors as well as parasite polymorphisms might influence the severity of malaria between susceptible and resistant mice.
Microbes and Infection, 2000
The rodent malaria parasite, Plasmodium yoelii nigeriensis is known to cause fatal malaria infections in BALB/c mice. However, we found that nearly 5% of inbred BALB/c mice could overcome primary infections initiated with lethal inoculum of P. y. nigeriensis asexual blood-stages, without any experimental intervention. These 'survivor' mice developed peak parasitemia levels of about 5% and successfully resolved their infections in about two weeks time; infected blood collected during the descending phase of infection in these mice and subinoculated in naive recipients resulted in a normal lethal course of infection. Typically, the parasites in survivor mice looked 'sick' compared to those in the susceptible mice. In experiments to define temporal basis of this protection, we found that purified splenic B cells isolated from such a survivor mouse, plus T cells from an infected or naive mouse, could adoptively transfer this protection to an X-irradiated, naive mouse against a lethal parasite challenge. Purified T cells or B cells alone from the survivor mouse donor provided no protection to the Xirradiated, naive recipient. Passive transfer of sera collected from survivor mice animals a week after recovery from infection was also able to substantially alter the course of preestablished P. y. nigeriensis infection. These findings are discussed in the light of recent reports on the genetic control of blood parasitemia in mouse malaria models. In the generally lethal malaria infections such as those caused by P. y. nigeriensis in mice and by Plasmodium falciparum in naive children, it is not clear what constitutes a protective immune response in cases which survive primary infections without any experimental or therapeutic intervention. An understanding of these mechanisms and their regulation would help design better vaccination strategies.
Parasite load stemming from immunization route determines the duration of liver‐stage immunity
Parasite Immunology, 2019
SummaryImmunization with radiation‐attenuated Plasmodium sporozoites (RAS) induces sterile and long‐lasting protective immunity. Although intravenous (IV) route of RAS immunization is reported to induce superior immunity compared to intradermal (ID) injection, its role in the maintenance of sterile immunity is yet to be understood. We investigated whether the route of homologous sporozoite challenge of Plasmodium berghei (Pb) RAS‐immunized mice would influence the longevity of protection. C57BL/6 mice immunized with Pb‐RAS by IV were 100% protected upon primary IV/ID sporozoite challenge. In contrast, ID immunization resulted in 80% protection, regardless of primary challenge route. Interestingly, the route of primary challenge was found to bring difference in the maintenance of sterile protection. While IV Pb RAS‐immunized mice remained protected at all challenges regardless of the route of primary challenge, ID Pb‐RAS‐immunized mice receiving ID primary challenge became parasitaem...
Veterinary Immunology and Immunopathology, 1984
Immunity to Babesia in mice. II. Cross protection between various Babesia and Plasmodium species and its relevance to the nature of Babesia immunity. Vet. Immunol. Immunopathol., 5: 359-368. Mice immunized against B.rodhaini by means of a drug-controlled infection were subsequently resistant to infection with B°microti and B.ratti. In the reciprocal experiments the protection against B.rodhaini was less effective. B.rodhaini immunized mice were also considerably protected against P.vinckei infection, whereas protection against P.berqhei did not occur. Antibody determinations indicated that the heterologous protection cannot be explained by the occurrence of cross-reacting antibodies. Because of similarity with the non-specific suppression of babesiosis in BCG-infected mice, the same effector mechanism is postulated to explain the infection-induced homologous and heterologous protection. Unlike non-specifically induced protection, the induction of acquired resistance by means of a drug-controlled B.rodhaini infection is thymus-dependent.