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Wnt Signalling Regulates Leishmania donovani Infection

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Title Wnt Signalling Regulates
Leishmania donovani Infection
 
Creator Maity, Shreyasi
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description The parasite Leishmania donovani causes a potentially fatal disease known as visceral leishmaniasis (VL) or kala-azar. The ever-increasing appearance of drug-resistant strains of L. donovani further exacerbates the difficulties of the disease, which in turn calls for increased focus on the exploration of host factors that play a role in the host defense against VL. Therefore, we evaluated the significance of host Wnt5A in restricting experimental visceral leishmaniasis in a mouse model using both drug-sensitive and drug-resistant strains of L. donovani. We demonstrated that Wnt5A heterozygous (Wnt5A+/-) mice are more vulnerable to L. donovani infection than Wnt5A wild type (Wnt5A+/+) mice. This was illustrated by a higher liver and spleen Leishman Donovan Unit (LDU) count in Wnt5A+/- mice than Wnt5A+/+ mice, which correlates with an increased plasma gammaglobulin level, the prevalence of liver granuloma, disorganization of splenic white pulps, and reduction of reactive oxygen species (ROS). On the other hand, we observed that augmenting the Wnt5A signalling pathway through intravenous administration of recombinant Wnt5A (rWnt5A) before infection with L. donovani was able to prevent the establishment and progression of experimental VL. We found that inhibiting VL with Wnt5A is connected with the preservation of splenic architecture, maintenance of splenic macrophages, activation of T cells, the generation of ROS, and a bias toward proinflammatory cytokines. Additionally, we demonstrated that the administration of rWnt5A in L. donovani-infected RAW 264.7 macrophages cause a substantial decrease in infection burden which is associated with an increase in both cellular ROS and secreted IFN-γ/IL-10 ratio. Also, the administration of rWnt5A in infected mice significantly inhibits the development of an L. donovani infection which is linked to an increase in ROS associated with immune cells and an activated T cell profile. Overall, our results indicate that the host Wnt5A signalling can suppress the progression of experimental visceral leishmaniasis, irrespective of drug-sensitive and drug-resistant strains. Moreover, our findings shed light on the therapeutic potential of rWnt5A in preventing L. donovani infection and the advancement of experimental visceral leishmaniasis.
 
Date 2022
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2868/1/Thesis_Shreyasi_Maity.pdf
Maity, Shreyasi (2022) Wnt Signalling Regulates Leishmania donovani Infection. PhD thesis, UNIVERSITY OF CALCUTTA.
 
Relation http://www.eprints.iicb.res.in/2868/