Visceral Leishmaniasis: Immunoregulation of Host Response to Antileishmanial Chemotherapy and Immunochemotherapy
Various host immunologic mechanisms, largely T [Th1] cell-dependent, regulate the in vivo capacity to respond to antileishmanial chemotherapy. Using pentavalent antimony and amphotericin B as two distinct pharmacologic probes in L. donovani-infected mice, this project examines the host mechanisms that determine or can enhance initial in-vivo host responsiveness to chemotherapy, and/or regulate subsequent prevention of posttreatment relapse. The work is focused on the interaction of antileishmanial chemotherapy with amplified cytokine-induced macrophage activation, chemokine-induced granuloma assembly, CD4 and CD8 cell responses, activating and deactivating mechanisms (cytokines, receptors, intracellular signaling), and immunologic effects induced by chemotherapy itself. The goal of the project is to employ immunochemotherapy to improve treatment-induced outcome in visceral leishmaniasis - both the initial host response to chemotherapy and the long-term prevention of relapse in this intracellular protozoal infection.
For nearly four decades, Dr. Murray has been working in the area of leishmaniasis (a tropical disease), both in the laboratory and clinically. For 15 years, he carried out clinical treatment trials research in visceral leishmaniasis ("kala-azar") in India. The drug he and colleagues in India introduced and tested for the treatment of kala-azar, miltefosine, was approved by the FDA in March 2014 as the first effective oral agent for leishmaniasis (visceral, cutaneous and mucosal infection).