Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition
- Johns Hopkins Bloomberg School of Public Health, United States
- University of Pennsylvania, United States
- Leiden University Medical Center, Netherlands
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. Here, 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.
Article and author information
Author details
Ethics
Animal experimentation: All animal work was conducted in accordance with the recommendations by the Johns Hopkins University Animal Care and Use Committee (IACUC), under the IACUC-approved protocol #M011H467.
Copyright
© 2015, Hopp et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,422
- views
-
- 578
- downloads
-
- 115
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition
eLife 4:e07789.
https://doi.org/10.7554/eLife.07789
Further reading
-
- Epidemiology and Global Health
- Microbiology and Infectious Disease
eLife has published papers on many tropical diseases, including malaria, Ebola, leishmaniases, Dengue and African sleeping sickness.
-
- Immunology and Inflammation
- Microbiology and Infectious Disease
Pseudomonas aeruginosa (PA) is an opportunistic, frequently multidrug-resistant pathogen that can cause severe infections in hospitalized patients. Antibodies against the PA virulence factor, PcrV, protect from death and disease in a variety of animal models. However, clinical trials of PcrV-binding antibody-based products have thus far failed to demonstrate benefit. Prior candidates were derivations of antibodies identified using protein-immunized animal systems and required extensive engineering to optimize binding and/or reduce immunogenicity. Of note, PA infections are common in people with cystic fibrosis (pwCF), who are generally believed to mount normal adaptive immune responses. Here, we utilized a tetramer reagent to detect and isolate PcrV-specific B cells in pwCF and, via single-cell sorting and paired-chain sequencing, identified the B cell receptor (BCR) variable region sequences that confer PcrV-specificity. We derived multiple high affinity anti-PcrV monoclonal antibodies (mAbs) from PcrV-specific B cells across three donors, including mAbs that exhibit potent anti-PA activity in a murine pneumonia model. This robust strategy for mAb discovery expands what is known about PA-specific B cells in pwCF and yields novel mAbs with potential for future clinical use.
