Wnt5A Signaling Antagonizes Leishmania donovani Infection
| Autor: | Malini Sen, Shreyasi Maity, Arijit Chakraborty |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
biology
InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL Wnt signaling pathway Leishmania donovani RAC1 biology.organism_classification Leishmania Parasite load Virology Cell biology body regions 03 medical and health sciences 0302 clinical medicine Immune system embryonic structures parasitic diseases sense organs GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Actin Intracellular 030215 immunology |
| Popis: | Leishmania donovani, the causative agent for visceral leishmaniasis creates a niche within host immune cells to sustain itself. In light of the fact that Wnt5a utilizes a Rac1–NFκB circuitry for sustaining immune homeostasis in macrophages and alters actin assembly (Naskar.et.al 2014, Witze et.al 2008) we deciphered whether there is any influence of Wnt5a signaling on L. donovani infection. Upon infection of macrophages with L.donovani , we noted significant decrease in Wnt5a protein levels. Infection with both SAG sensitive and SAG resistant parasite strains yielded similar results. Interestingly, upon treatment of macrophages with recombinant Wnt5a prior to infection separately with SAG senstive and SAG resistant L.donovani , there was significant decrease in the intracellular load of both strains of parasite, as judged by microscopic analysis and expression of Leishmania specific genes (Amastin and G6PDH). Depleting Wnt5a from the macrophages by si-RNA in-vitro or by use of Inhibitor of Wnt Production (IWP2) in-vivo , on the other hand, led to an increase in parasite load. Using specific inhibitors of the Wnt5a signaling intermediates Rac1 and NFκB, we demonstrated that Wnt5a induced reduction in parasite load is due to Wnt5a dependent Rac1 activity but not NFκB signalling. In light of the known involvement of Rac1 in actin organization, the altered actin assembly of Wnt5a pre-treated macrophages, as evident from flow cytometric analysis corroborated the observed Rac1 mediated inhibition of L.donovani infection. Taken together, our results indicate that (i) Wnt5a signaling is detrimental to L. donovani infection and (ii) the parasite evades host immune response at least partly through obliteration of Wnt5a signaling. |
| Databáze: | OpenAIRE |
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