Activation of the NLRP3 inflammasome has been shown to play a major role in the neuroinflammation that accompanies Alzheimer’s disease (AD); interventions that down regulate the NLRP3 inflammasome could thus be beneficial in AD. Parasite infections were recently shown to be associated with improved cognitive functions in Apolipoprotein E4 (ApoE4)-expressing members of an Amazonian tribe. We verified in an in vitro model whether Leishmania infantum infection could reduce NLRP3. Results obtained in an initial experimental model in which PBMC were LPS primed and nigericin-stimulated showed that L. infantum infection significantly reduced ASC-speck formation (i.e. intracellular inflammasome proteins assembly), as well as the production of activated caspase 5 and IL-1β, but increased that of activated caspase 1 and IL-18. Moreover, L. infantum infection induced the generation of an anti-inflammatory milieu by suppressing the production of TNFα and increasing that of IL-10. These results were replicated when cells that had been LPS-primed were stimulated with Aβ42 and infected with L. infantum.. Results herein indicate that Leishmania infection favors an anti-inflammatory milieu, which includes the down-regulation of NLRP3 inflammasome activation, possibly to facilitate its survival inside host cells. A side effect of Leishmaniasis would be the hampering of neuroinflammation; this could play a protective role against AD development.

Leishmania infantum infection reduces the amyloid β42-stimulated NLRP3 inflammasome activation

La Rosa, Francesca;Banks, Helen;
2020

Abstract

Activation of the NLRP3 inflammasome has been shown to play a major role in the neuroinflammation that accompanies Alzheimer’s disease (AD); interventions that down regulate the NLRP3 inflammasome could thus be beneficial in AD. Parasite infections were recently shown to be associated with improved cognitive functions in Apolipoprotein E4 (ApoE4)-expressing members of an Amazonian tribe. We verified in an in vitro model whether Leishmania infantum infection could reduce NLRP3. Results obtained in an initial experimental model in which PBMC were LPS primed and nigericin-stimulated showed that L. infantum infection significantly reduced ASC-speck formation (i.e. intracellular inflammasome proteins assembly), as well as the production of activated caspase 5 and IL-1β, but increased that of activated caspase 1 and IL-18. Moreover, L. infantum infection induced the generation of an anti-inflammatory milieu by suppressing the production of TNFα and increasing that of IL-10. These results were replicated when cells that had been LPS-primed were stimulated with Aβ42 and infected with L. infantum.. Results herein indicate that Leishmania infection favors an anti-inflammatory milieu, which includes the down-regulation of NLRP3 inflammasome activation, possibly to facilitate its survival inside host cells. A side effect of Leishmaniasis would be the hampering of neuroinflammation; this could play a protective role against AD development.
2020
2020
Saresella, Marina; Basilico, Nicoletta; Marventano, Ivana; Perego, Federica; La Rosa, Francesca; Piancone, Federica; Taramelli, Donatella; Banks, Helen; Clerici, Mario
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11565/4025989
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