Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria.
BACKGROUND
To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/c mice succumbing to infection with Plasmodium chabaudi were compared to those surviving after vaccination.


METHODS
Mice were vaccinated with host cell plasma membranes isolated from P. chabaudi-infected erythrocytes. Hepatic and splenic capacity to trap particulate material was determined after injection of fluorescent polystyrol beads. Hepatic gene expression was measured using real-time RT-PCR and Northern blotting.


RESULTS
Survival of BALB/c mice was raised from 0% to 80% and peak parasitaemia was decreased by about 30% by vaccination. Vaccination boosted particle trapping capacity of the liver during crisis when splenic trapping is minimal due to spleen 'closing'. It also attenuated malaria-induced inflammation, thus diminishing severe damages and hence liver failure. Vaccination increased hepatic IFN-gamma production but mitigated acute phase response. Vaccination has a complex influence on infection-induced changes in expression of hepatic nuclear receptors (CAR, FXR, RXR, and PXR) and of the metabolic enzymes Sult2a and Cyp7a1. Although vaccination decreased CAR mRNA levels and prevented Cyp7a1 suppression by the CAR ligand 1,2-bis [2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) on day 8 p.i., Sult2a-induction by TCPOBOP was restored.


CONCLUSIONS
These data support the view that the liver is an essential effector site for a vaccine against blood stage malaria: vaccination attenuates malaria-induced inflammation thus improving hepatic metabolic activity and particle trapping activity of the liver.
Krücken
Jürgen
J
Institute for Parasitology, University of Veterinary Medicine Foundation, Hannover, Germany. juergen.kruecken@tiho-hannover.de
Delić
Denis
D
Pauen
Heike
H
Wojtalla
Anna
A
El-Khadragy
Manal
M
Dkhil
Mohamed A
MA
Mossmann
Horst
H
Wunderlich
Frank
F