Fernández Ruiz, Daniel: Filarial nematodes protect against malaria in a murine co-infection model. - Bonn, 2008. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5N-15245
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5N-15245,
author = {{Daniel Fernández Ruiz}},
title = {Filarial nematodes protect against malaria in a murine co-infection model},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2008,
note = {

Helminth infections such as filariasis can be life long due to immunomodulatory mechanisms elicited by the worms that prevent their elimination by the human host. Malaria prevalence is frequently high in areas where filarial nematode infections are endemic, originating co-infections. It is still an ongoing debate the extent to which worms can alter anti-plasmodial responses in a concomitantly infected host. In order to dissect the interactions occurring between both parasites, a murine model using the filarial nematode Litomosoides sigmodontis and the malaria parasite Plasmodium berghei ANKA in BALB/c and C57BL/6 mice has been established in the present work.
One third of helminth-infected BALB/c mice remained malaria negative and did not develop detectable parasitaemia after co-infection with plasmodial sporozoites. Such outcomes were not observed after co-infection with blood stage parasites, thereby circumventing the plasmodial liver stage, but were only originated after sporozoite inoculation. Protection depended on IL-10, since IL-10 deficient co-infected mice were fully susceptible to sporozoite challenge. However, systemic IL-10 levels were low, suggesting a local function of this cytokine. 44 h after P. berghei sporozoite inoculation increased CD8+ T cell numbers were found in the liver and spleen of co-infected mice. Interestingly, protection as well as numbers of CD8+ T cells correlated with the presence of microfilaraemia. Since microfilariae are potent stimulators of immune responses, their presence in the blood may enhance cross-protective responses against incoming sporozoites.
Co-infected C57BL/6 mice showed significantly reduced cerebral malaria (CM) rates. CD8+ T cell recruitment to brain, a critical condition for CM development, was reduced in co-infected mice. Furthermore, in contrast to P. berghei single-infected animals, groups of double infected mice presented high levels of circulating IL-10. The absolute requirement for IL-10 in CM protection was demonstrated by the total susceptibility to the pathology in IL-10 KO co-infected mice. Hence IL-10-dependent immunoregulatory mechanisms elicited by filarial nematodes might be able to suppress the overwhelming inflammatory reaction usually triggered against malaria parasites by C57BL/6 mice, preventing full progress to CM.
Taken together, this work shows that depending on the genetic background different mechanisms elicited by filarial worms improve control of both liver and blood stages of concomitant malaria parasites, and moreover ameliorate severe pathology in a murine model. The main beneficial effects driven by filariae rely on IL-10, which on the one hand prevents CM through immunomodulation but on the other enhances protective anti-malarial responses in the liver. Worm eradication programs are currently being carried out in endemic countries, but this study suggests that their implementation may cause unpredictable consequences on malaria control.


url = {https://hdl.handle.net/20.500.11811/3674}

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