Limits...
Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition.

Hopp CS, Chiou K, Ragheb DR, Salman A, Khan SM, Liu AJ, Sinnis P - Elife (2015)

Bottom Line: How sporozoites locate and enter a blood vessel is a critical, but poorly understood process.Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit 'avascular motility', defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained.Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.

ABSTRACT
Malaria infection starts with injection of Plasmodium sporozoites by an Anopheles mosquito into the skin of the mammalian host. How sporozoites locate and enter a blood vessel is a critical, but poorly understood process. In this study, we examine sporozoite motility and their interaction with dermal blood vessels, using intravital microscopy in mice. Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit 'avascular motility', defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained. We find that curvature of sporozoite tracks engaging with vasculature optimizes contact with dermal capillaries. Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site.

No MeSH data available.


Related in: MedlinePlus

Motility is increasingly constrained over time after sporozoite inoculation by mosquito bite.A mosquito infected with PbmCherry sporozoites was allowed to probe on the ear pinnae of an anethesized mouse and the first 4-min time-lapse was acquired 3 min after the proboscis was seen in the field of view. The bite site was followed for a total of 110 min, and images were acquired at the indicated times. Data shown was obtained from two biological replicate time courses. (A) Sporozoites were manually tracked using Imaris software to compare the MSD of sporozoites at 3 min (38 tracks), 10 min (30 tracks), 20 min (73 tracks), 40 min (53 tracks), 60 min (61 tracks), and 110 min (1 video only/21 tracks) after mosquito bite. (B) Proportion of manually counted sporozoite motility patterns are shown as percent of total sporozoites. Data from two independent experiments are shown.DOI:http://dx.doi.org/10.7554/eLife.07789.006
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4594146&req=5

fig1s2: Motility is increasingly constrained over time after sporozoite inoculation by mosquito bite.A mosquito infected with PbmCherry sporozoites was allowed to probe on the ear pinnae of an anethesized mouse and the first 4-min time-lapse was acquired 3 min after the proboscis was seen in the field of view. The bite site was followed for a total of 110 min, and images were acquired at the indicated times. Data shown was obtained from two biological replicate time courses. (A) Sporozoites were manually tracked using Imaris software to compare the MSD of sporozoites at 3 min (38 tracks), 10 min (30 tracks), 20 min (73 tracks), 40 min (53 tracks), 60 min (61 tracks), and 110 min (1 video only/21 tracks) after mosquito bite. (B) Proportion of manually counted sporozoite motility patterns are shown as percent of total sporozoites. Data from two independent experiments are shown.DOI:http://dx.doi.org/10.7554/eLife.07789.006

Mentions: Our analysis shows that the change in sporozoite trajectories at 20 and 30 min was not due to their slowing down (Figure 1D and Figure 1—figure supplement 1). To better understand this increase in parasite confinement, track straightness was calculated. Track straightness is defined as the ratio of displacement to track length (Beltman et al., 2009), and smaller ratios reflect more constrained tracks, while straight tracks are characterized by large ratios. This analysis included the entire population of motile sporozoites (meandering sporozoites, as well as sporozoites continuously moving in the same circle). As shown in Figure 1F, the straightness of sporozoite tracks gradually decreases over the first 120 min after inoculation with the most significant decrease seen beginning at 20 min after inoculation. These data suggest that sporozoite motility changes over time such that after an initial phase of maximal dispersal, sporozoites move in more constrained circular paths. Of note, a similiar change in sporozoite motility was seen in data acquired from sporozoites imaged after inoculation by a probing infected mosquito, with a significant drop in MSD 20 min after mosquito bite and a concomitant increase in the number of sporozoites engaging in circular motility (see Figure 1—figure supplement 2). Though these data suggest that overall, the pattern of motility is similar whether sporozoites are deposited by mosquito bite or needle; additional experimentation is needed to provide more quantitative data. Unfortunately, these data are more difficult to acquire because of technical issues in finding and capturing, by video-microscopy, sporozoites inoculated by a probing mosquito.


Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition.

Hopp CS, Chiou K, Ragheb DR, Salman A, Khan SM, Liu AJ, Sinnis P - Elife (2015)

Motility is increasingly constrained over time after sporozoite inoculation by mosquito bite.A mosquito infected with PbmCherry sporozoites was allowed to probe on the ear pinnae of an anethesized mouse and the first 4-min time-lapse was acquired 3 min after the proboscis was seen in the field of view. The bite site was followed for a total of 110 min, and images were acquired at the indicated times. Data shown was obtained from two biological replicate time courses. (A) Sporozoites were manually tracked using Imaris software to compare the MSD of sporozoites at 3 min (38 tracks), 10 min (30 tracks), 20 min (73 tracks), 40 min (53 tracks), 60 min (61 tracks), and 110 min (1 video only/21 tracks) after mosquito bite. (B) Proportion of manually counted sporozoite motility patterns are shown as percent of total sporozoites. Data from two independent experiments are shown.DOI:http://dx.doi.org/10.7554/eLife.07789.006
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4594146&req=5

fig1s2: Motility is increasingly constrained over time after sporozoite inoculation by mosquito bite.A mosquito infected with PbmCherry sporozoites was allowed to probe on the ear pinnae of an anethesized mouse and the first 4-min time-lapse was acquired 3 min after the proboscis was seen in the field of view. The bite site was followed for a total of 110 min, and images were acquired at the indicated times. Data shown was obtained from two biological replicate time courses. (A) Sporozoites were manually tracked using Imaris software to compare the MSD of sporozoites at 3 min (38 tracks), 10 min (30 tracks), 20 min (73 tracks), 40 min (53 tracks), 60 min (61 tracks), and 110 min (1 video only/21 tracks) after mosquito bite. (B) Proportion of manually counted sporozoite motility patterns are shown as percent of total sporozoites. Data from two independent experiments are shown.DOI:http://dx.doi.org/10.7554/eLife.07789.006
Mentions: Our analysis shows that the change in sporozoite trajectories at 20 and 30 min was not due to their slowing down (Figure 1D and Figure 1—figure supplement 1). To better understand this increase in parasite confinement, track straightness was calculated. Track straightness is defined as the ratio of displacement to track length (Beltman et al., 2009), and smaller ratios reflect more constrained tracks, while straight tracks are characterized by large ratios. This analysis included the entire population of motile sporozoites (meandering sporozoites, as well as sporozoites continuously moving in the same circle). As shown in Figure 1F, the straightness of sporozoite tracks gradually decreases over the first 120 min after inoculation with the most significant decrease seen beginning at 20 min after inoculation. These data suggest that sporozoite motility changes over time such that after an initial phase of maximal dispersal, sporozoites move in more constrained circular paths. Of note, a similiar change in sporozoite motility was seen in data acquired from sporozoites imaged after inoculation by a probing infected mosquito, with a significant drop in MSD 20 min after mosquito bite and a concomitant increase in the number of sporozoites engaging in circular motility (see Figure 1—figure supplement 2). Though these data suggest that overall, the pattern of motility is similar whether sporozoites are deposited by mosquito bite or needle; additional experimentation is needed to provide more quantitative data. Unfortunately, these data are more difficult to acquire because of technical issues in finding and capturing, by video-microscopy, sporozoites inoculated by a probing mosquito.

Bottom Line: How sporozoites locate and enter a blood vessel is a critical, but poorly understood process.Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit 'avascular motility', defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained.Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.

ABSTRACT
Malaria infection starts with injection of Plasmodium sporozoites by an Anopheles mosquito into the skin of the mammalian host. How sporozoites locate and enter a blood vessel is a critical, but poorly understood process. In this study, we examine sporozoite motility and their interaction with dermal blood vessels, using intravital microscopy in mice. Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit 'avascular motility', defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained. We find that curvature of sporozoite tracks engaging with vasculature optimizes contact with dermal capillaries. Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site.

No MeSH data available.


Related in: MedlinePlus