Comparative intravital imaging of human and rodent malaria sporozoites reveals the skin is not a species‐specific barrier

ABSTRACT In regions where malaria is endemic, inhabitants remain susceptible to repeated reinfection as they develop and maintain clinical immunity. This immunity includes responses to surface-exposed antigens onPlasmodium sp.-infected erythrocytes. Some of these parasite-encoded antigens may be diverse and phenotypically variable, and the ability to respond to this diversity and variability is an important component of acquired immunity. Characterizing the relative specificities of antibody responses during the acquisition of immunity and in hyperimmune individuals is thus an important adjunct to vaccine research. This is logistically difficult to do in the field but is relatively easily carried out in animal models. Infections in inbred mice with rodent malaria parasite Plasmodium chabaudi chabaudi AS represent a good model for Plasmodium falciparum in humans. This model has been used in the present study in a comparative analysis of cross-reactive and specific immune responses in rodent malaria. CBA/Ca mice were rendered hyperimmune toP. chabaudi chabaudi (AS or CB lines) or Plasmodium berghei (KSP-11 line) by repeated infection with homologous parasites. Serum from P. chabaudi chabaudi AS hyperimmune mice reacted with antigens released from disrupted P. chabaudi chabaudi AS-infected erythrocytes, but P. chabaudi chabaudi CB and P. berghei KSP-11 hyperimmune serum also contained cross-reactive antibodies to these antigens. However, antibody activity directed against antigens exposed at the surfaces of intact P. chabaudi chabaudi-infected erythrocytes was mainly parasite species specific and, to a lesser extent, parasite line specific. Importantly, this response included opsonizing antibodies, which bound to infected erythrocytes, leading to their phagocytosis and destruction by macrophages. The results are discussed in the context of the role that antibodies to both variable and invariant antigens may play in protective immunity in the face of continuous susceptibility to reinfection.

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Quantitative intravital imaging of Plasmodium falciparum sporozoites: A novel platform to test malaria intervention strategies

10.1101/716878 ◽

2019 ◽

Cited By ~ 2

Author(s):

Christine S. Hopp ◽

Sachie Kanatani ◽

Nathan K. Archer ◽

Robert J. Miller ◽

Haiyun Liu ◽

...

Keyword(s):

Xenograft Model ◽

Mouse Skin ◽

Intervention Strategies ◽

Rodent Malaria ◽

Human Malaria ◽

Drug Candidates ◽

Detection And Tracking ◽

Species Specific ◽

Skin Xenograft

AbstractMalaria infection starts with the injection of motile Plasmodium sporozoites into the host’s skin during a mosquito bite. Previous studies using the rodent malaria model indicate that the dermal inoculation site may be where sporozoites are most vulnerable to antibodies, yet, functional in vivo assays with human malaria parasites are lacking. Here, we present the first characterization of P. falciparum sporozoites in the skin, comparing their motility to two rodent malaria species and investigating whether the environment of its natural host influences P. falciparum sporozoite motility using a human skin xenograft model. The combined data suggest that in contrast to the liver and blood stages, the skin is not a species-specific barrier for Plasmodium. We observe that P. falciparum sporozoites inoculated into mouse skin move with similar speed, displacement and duration, and enter blood vessels in similar numbers as the rodent parasites. Thus, interventions targeting P. falciparum sporozoite migration can be tested in the murine dermis. Importantly, to streamline quantification of sporozoite motility, we developed a toolbox allowing for automated detection and tracking of sporozoites in intravital microscopy videos. This establishes a platform to test vaccine candidates, immunization protocols, monoclonal antibodies and drug candidates for their impact on human malaria sporozoites in vivo. Screening of intervention strategies for in vivo efficacy against Pf sporozoites using this new platform will have the potential to validate targets prior to expensive clinical trials.

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Use of a DNA probe to analyse the dynamics of infection with rodent malaria parasites confirms that parasite clearance during crisis is predominantly strain- and species-specific

Molecular and Biochemical Parasitology ◽

10.1016/0166-6851(89)90100-x ◽

1989 ◽

Vol 37 (1) ◽

pp. 37-46 ◽

Cited By ~ 22

Author(s):

G SNOUNOU ◽

W JARRA ◽

S VIRIYAKOSOL ◽

J WOOD ◽

K BROWN

Keyword(s):

Parasite Clearance ◽

Dna Probe ◽

Malaria Parasites ◽

Rodent Malaria ◽

Species Specific

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Electron Microscopy in the Study of Natural Phytoplankton Assemblages

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119831 ◽

1985 ◽

Vol 43 ◽

pp. 620-623

Author(s):

Linda Sicko-Goad

Keyword(s):

Electron Microscopy ◽

Aquatic Environment ◽

Size Range ◽

Physical Parameters ◽

Specific Information ◽

Phytoplankton Assemblages ◽

Phytoplankton Productivity ◽

Ecosystem Effects ◽

Time Of Year ◽

Species Specific

Although the use of electron microscopy and its varied methodologies is not usually associated with ecological studies, the types of species specific information that can be generated by these techniques are often quite useful in predicting long-term ecosystem effects. The utility of these techniques is especially apparent when one considers both the size range of particles found in the aquatic environment and the complexity of the phytoplankton assemblages.The size range and character of organisms found in the aquatic environment are dependent upon a variety of physical parameters that include sampling depth, location, and time of year. In the winter months, all the Laurentian Great Lakes are uniformly mixed and homothermous in the range of 1.1 to 1.7°C. During this time phytoplankton productivity is quite low.

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