Wednesday, April 08, 2015

AMA1-deficient Toxoplasma parasites transiently colonize mice and trigger an innate immune response that proceeds to long lasting protective immunity

2015 Apr 6. pii: IAI.02606-14. [Epub ahead of print]
The Apical Membrane Antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera Plasmodium and Toxoplasma, until we genetically engineered viable parasites lacking AMA1. The reduction in invasiveness of the T. gondii RH-AMA1KO tachyzoite population, in vitro, raised key questions about the outcome of these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used the AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1KO tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leucocytes. While the RH-AMA1KO population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts where a combination of immune cells sense parasites and secrete pro-inflammatory cytokines. This innate response further leads to a long-lasting immunoprotective status against a secondary challenge by high inocula of the homologous type I or a distinct type II T. gondii genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population in vivo.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
[PubMed - as supplied by publisher]

No comments: