ELUCIDATING THE ROLE OF CD47 IN AMELIORATING CUTANEOUS LEISHMANIASIS - ABSTRACT LEISHMANIA MAJOR (L. MAJOR) IS A MAJOR CAUSATIVE SPECIES OF CUTANEOUS LEISHMANIASIS (CL). CL IS THE MOST COMMON FORM OF LEISHMANIASIS, RESPONSIBLE FOR GREATER THAN 90% OF REPORTED CASES. CURRENT TREATMENTS FOR CL, COMMONLY CONSISTING OF INTRALESIONAL INJECTIONS OF PENTAVALENT ANTIMONIALS, ARE HARSH AND NOT WIDELY ACCESSIBLE IN HIGHLY ENDEMIC AREAS. WHILE L. MAJOR LESIONS IN OTHERWISE HEALTHY PATIENTS WILL TYPICALLY HEAL SPONTANEOUSLY IN 2-12 MONTHS, PROLONGED OPEN LESIONS RESULT IN WORSE SCARRING AND OTHER POTENTIAL COMPLICATIONS LIKE SECONDARY INFECTION. WITH UPWARD ESTIMATES OF 1.2 MILLION NEW GLOBAL CASES OF CL EVERY YEAR, THERE IS A CRITICAL NEED TO UNDERSTAND FACTORS THAT ALLOW L. MAJOR TO SURVIVE, PERSIST, AND PROLIFERATE WITHIN A HOST. ONGOING WORK IN OUR LAB HAS SHOWN A STRONG ROLE FOR THE CD47-SIRP CO-RECEPTORS, ALSO KNOWN AS THE "DON'T EAT ME" SIGNAL, IN MEDIATING RESISTANCE OF C57BL/6 MICE TO L. MAJOR INFECTION. WE FIND THAT IN THE ABSENCE OF CD47 OR SIRP, MICE ARE HIGHLY SUSCEPTIBLE TO L. MAJOR INFECTION. WE HAVE DEMONSTRATED THAT L.MAJOR INFECTED CD47-/- BONE MARROW DERIVED MACROPHAGES (BMDM) ARE MORE RESISTANT TO L.MAJOR MEDIATED CELL DEATH THAN CONTROLS. IN VIVO WE HAVE REDUCED T CELL EFFECTOR FUNCTIONS AT CHRONIC TIMEPOINTS. MOST NOTABLY, WE OBSERVE A REDUCTION IN IFN AND TNF, BOTH OF WHICH ARE CYTOKINES CRITICAL FOR RESOLUTION OF L. MAJOR INFECTION. HERE WE PROPOSE A SERIES OF STUDIES TO EVALUATE WHERE EXPRESSION OF CD47 AND SIRP ARE REQUIRED TO MEDIATE PROTECTION, AS WELL AS EXPERIMENTS TO DETERMINE MECHANISTICALLY HOW THE "DON'T EAT ME" SIGNAL PROMOTES RESISTANCE TO L. MAJOR INFECTION.