The role of toll-like receptor agonists in the immunotherapy of leishmaniosis. An update and proposal for a new form of anti-leishmanial therapy

The use of toll-like receptor agonists in immunotherapy is a new approach in the prevention of immunosuppression during fatal Leishmania parasite infection. The objective of such immunotherapy is to activate specific cell-mediated immune responses, macrophage activation and antigen-responsive inflammation, to kill intracellular amastigotes. Toll-like receptor agonist-based treatment in immunocompetent hosts can be effective either by selective use of the agonists alone or in combination with the anti-leishmanial drug stibanate. Recent investigations suggest that toll-like receptor signal pathways constitute a possible new mode of anti-leishmanial treatment. This article describes the prospect of toll-like receptor – mediated signal pathways in the immunotherapy of cutaneous and visceral leishmaniosis, as well as post kala-azar dermal leishmaniosis (PKADL), a skin-sequel of visceral infection. Suitable synthetic agonists need to be developed for toll-like receptors to overcome immunosuppression

Immunosuppression during Leishmania donovani infection: a potential target for the development of therapy

Dysfunction of T-helper 1 mediated immune responses is a hallmark of the progression of visceral leishmaniosis (VL). Several factors such as altered antigen presentation, and abnormalities in MHC/HLA, antigen processing, and T cell receptor recognition regulate the onset of immunosuppression. Recent investigations on VL patients suggest that susceptibility to visceral leishmaniosis is genetically determined and varies between populations in different geographical locations. Emerging evidence also indicates the importance of the role played by myeloid derived suppressor cells in progressive VL. This study provides a mechanistic view of means to target the signaling mechanisms of immunosuppression to determine potential therapeutic interventions