Role of host cellular response in differential susceptibility of nonimmunized BALB/c mice to Plasmodium berghei and Plasmodium yoelii sporozoites

Abstract

We found BALB/c mice to be on the order of 2,000 times more susceptible to Plasmodium yoelii than Plasmodium berghei sporozoites, as measured by the ability of these sporozoites to differentiate into microscopically detectable hepatic schizonts in the livers of immunologically naive mice. One of the factors that determine the relative insusceptibility of mice to P. berghei sporozoites is the innate cellular inflammatory response that the mice mount after injection with sporozoites. The cellular inflammatory response against P. berghei is initiated soon after sporozoite injection; by 24 h, substantial histopathological changes have developed within the liver. There is considerably less of a cellular inflammatory response against P. yoelii; significant histopathological changes within the liver are not observed until well after hepatic schizonts have begun to rupture at around 44 h postinjection of sporozoites. These differences in the cellular inflammatory response against two different, closely related species of sporozoites are of considerable interest. The data strongly suggest that the BALB/c-P. berghei sporozoite system is a relatively poor biological model for sporozoite immunization studies.

Quantitative intravital imaging ofPlasmodium falciparumsporozoites: A novel platform to test malaria intervention strategies

“…These data suggest that P. yoelii sporozoites have a longer period of time during which they are infectious post-inoculation. While previous studies using intravenously inoculated sporozoites demonstrated that P. yoelii sporozoites develop better in the liver compared to P. berghei (16)(17)(18)(19), our results suggest that the higher infectivity of P. yoelii sporozoites is also due to their behavior in the skin, further supporting the notion that sporozoite motility in the dermis is a valid correlate for infectivity of the parasite. Recently a number of transgenic rodent parasite lines expressing P. falciparum or P. vivax CSP have been developed for pre-clinical vaccine testing in the rodent model (27)(28)(29).…”

“…Interestingly, while for both P. berghei and P. falciparum, these high-displacing sporozoites are no longer observed at 60 min after inoculation ( Figure 3D and 3F), P. yoelii sporozoites are still moving larger distances, with 3% of sporozoites moving between 50-200 μm in displacement at 60 and 120 min after inoculation ( Figure 3E). This difference in sporozoite behavior between the two rodent Plasmodium species is consistent with previous studies which showed that the infectivity of P. yoelii sporozoites to rodents is significantly higher than that of P. berghei sporozoites (16)(17)(18)(19) and is in line with the observation of a persistent exit of P. yoelii sporozoites out of the dermis into the circulation for over 2 hours after inoculation (10).…”

“…We found that compared to P. berghei, which, over the course of two hours, lose the ability to move in the dermis, the percentage of motile P. yoelii and P. falciparum does not rapidly drop off and remains similar at later time points, with 30% to 20% of sporozoites moving at 60 to 120 min after inoculation, respectively. This is consistent with the observation of a slow trickle of P. yoelii sporozoites out of the dermis over more than 3 hours after inoculation (10) and suggests that the observed higher infectivity of P. yoelii sporozoites compared to P. berghei may reflect their biology in the skin in addition to their increased infectivity in the liver (10,(16)(17)(18)(19).…”

Plasmodium sporozoites trickle out of the injection site

“…In the following experiments we used the rodent parasite Plasmodium yoelii because infectivity of its sporozoites to laboratory rodents is significantly higher than that of P. berghei (Weiss, 1990;Khan and Vanderberg, 1991;Khusmith et al, 1991), thus allowing us to conduct meaningful quantitative studies of hepatic parasite loads. We first wished to establish the kinetics of sporozoite exit out of the inoculation site.…”

Susceptibility of different strains of mice to hepatic infection with Plasmodium berghei

“…Data gathered from different mouse strains concerning the irradiated-attenuated sporozoite vaccine (4,15) were useful for designing vaccine trials in humans (2,3,(7)(8)(9)17). Previous studies have shown that BALB/c mice have a low susceptibility to P. berghei hepatic infection; only 0.01% of inoculated sporozoites infect the liver (13). This low susceptibility was correlated with the ability of BALB/c mice to elicit a cellular inflammatory response against the EE stages of P. berghei.…”