Author:
Gupta Anuj,Styczynski Mark P.,Galinski Mary R.,Voit Eberhard O.,Fonseca Luis L.
Abstract
AbstractPlasmodium knowlesi, a model malaria parasite, is responsible for a significant portion of zoonotic malaria cases in Southeast Asia and must be controlled to avoid disease severity and fatalities. However, little is known about the host-parasite interactions and molecular mechanisms in play during the course of P. knowlesi malaria infections, which also may be relevant across Plasmodium species. Here we contrast P. knowlesi sporozoite-initiated infections in Macaca mulatta and Macaca fascicularis using whole blood RNA-sequencing and transcriptomic analysis. These macaque hosts are evolutionarily close, yet malaria-naïve M. mulatta will succumb to blood-stage infection without treatment, whereas malaria-naïve M. fascicularis controls parasitemia without treatment. This comparative analysis reveals transcriptomic differences as early as the liver phase of infection, in the form of signaling pathways that are activated in M. fascicularis, but not M. mulatta. Additionally, while most immune responses are initially similar during the acute stage of the blood infection, significant differences arise subsequently. The observed differences point to prolonged inflammation and anti-inflammatory effects of IL10 in M. mulatta, while M. fascicularis undergoes a transcriptional makeover towards cell proliferation, consistent with its recovery. Together, these findings suggest that timely detection of P. knowlesi in M. fascicularis, coupled with control of inflammation while initiating the replenishment of key cell populations, helps contain the infection. Overall, this study points to specific genes and pathways that could be investigated as a basis for new drug targets that support recovery from acute malaria.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Defense Advanced Research Projects Agency
Publisher
Springer Science and Business Media LLC
Reference106 articles.
1. World Health Organization. World Malaria Report (2019).
2. Harper, K. & Armelagos, G. The changing disease-scape in the third epidemiological transition. Int. J. Environ. Res. Public Health 7, 675–697. https://doi.org/10.3390/ijerph7020675 (2010).
3. Division of Parasitic Diseases and Malaria (CDC). The History of Malaria, an Ancient Disease https://www.cdc.gov/malaria/about/history/index.html (2017).
4. Karunamoorthi, K. Malaria vaccine: A future hope to curtail the global malaria burden. Int. J. Prev. Med. 5, 529–538 (2014).
5. Kirchner, S., Power, B. J. & Waters, A. P. Recent advances in malaria genomics and epigenomics. Genome Med. 8, 92. https://doi.org/10.1186/s13073-016-0343-7 (2016).
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