Ceramide In The Establishment Of Visceral Leishmaniasis, An Insight Into Membrane Architecture And Pathogenicity

Biological membranes are the permeability barrier for the selective entry of biomolecules but sometimes they are responsible for providing platform for the entry and establishment of infection. Sphingomyelins are the chief component of the most biological membranes, ceramide being one of its important componenst. Generation of ceramide leads to increased susceptibility of the host towards parasite. Increased endogenous ceramide resulted into elevated expression of PKC sigma which causes down-regulation of essential component of MAPK pathways including p-38, JNK and on the other hand increases the phosphorylation of ERK1/2. Alternative activation of different MAPKs ultimately leads to reduced nuclear translocation of NF kappa B and AP-1 as a result of which the cell show increased synthesis of immunosuppressive cytokines such as TGF-beta and IL-10 along with reduced NO generation, leading to severe host immune suppression. On the other hand ceramide also induced by de novo pathway which further shows increased membrane fluidity and hampered antigen presentation and reciprocal regulation of different T-cell subsets including T-reg and Th-17 cells. Collectively the roles of ceramide in infectious diseases is of great importance and can be a specific target for designing therapy against infection.