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Dr Eva Hesping – Infectious Diseases & Immune Defence division

10/07/2024 1:00 pm - 10/07/2024 2:00 pm
Location
Davis Auditorium

WEHI Wednesday Seminar hosted by Associate Professor Justin Boddey
 

Dr Eva Hesping

Research Officer – Boddey Laboratory, Infectious Diseases & Immune Defence division – Infection, Inflammation & Immunity Theme, WEHI

 

Plasmepsin V is essential for Plasmodium liver stage development via suppression of innate immunity 

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

 

 

Liver stage malaria represents the initial phase of malaria infection, where Plasmodium exoerythrocytic forms (EEFs) develop within hepatocytes before progressing to the symptomatic blood stage. Plasmodium parasites release proteins into erythrocytes, altering the host cell to control their development and survival, involving the cleavage of the Plasmodium export element (PEXEL) by Plasmepsin V. However, the precise role of protein export and Plasmepsin V during liver stage malaria remains unclear.

 

We generated Plasmepsin V knockdown sporozoites and despite their ability to invade hepatocytes, we observed a reduction in parasite fitness 6-24 hours post-infection. Mice infected with PMV knockdown EEFs showed lower parasite liver burdens and delayed prepatent periods. Dual RNA-sequencing revealed that over 80% of the parasite’s genes that encode for putatively exported proteins (PEXEL) were transcribed during the 6-44 hours post hepatocyte infection window, peaking at 6-14 hours post-infection. Additionally, differential expression of genes encoding exported proteins was observed between PMV knockdown and wildtype EEFs.

 

Furthermore, wildtype EEFs downregulated long non-coding RNAs (lncRNAs) known to trigger innate immune responses, whereas PMV knockdown parasites significantly upregulated these lncRNAs, leading to rapid parasite elimination. Our study highlights the importance of PMV activity in Plasmodium liver infection and suggests a potential role for lncRNAs in promoting immunity against malaria parasites.

 

 

All welcome!

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