Document Type


Date of Degree Completion

Fall 2018

Degree Name

Master of Science (MS)



Committee Chair

Gabrielle Stryker

Second Committee Member

Blaise Dondji

Third Committee Member

Wayne Quirk


Leishmaniasis is a parasitic disease caused by protozoans of the genus Leishmania. This vector-born disease, transmitted by biting phlebotomine sandflies, typically manifests in one of three ways. The cutaneous form of the disease is characterized by localized lesions of the skin and is by far the most common manifestation. The visceral form of the disease is caused by parasitic infiltration of internal organs, particularly the spleen, liver, and bone marrow. The mucocutaneous form is caused by parasitic infection of the mucosa in the nose or mouth. While cutaneous leishmaniasis (CL) is often self-healing, visceral leishmaniasis (VL) is fatal if left untreated. Mucocutaneous leishmaniasis (MCL) can lead to severe facial disfigurement if left untreated but is not particularly deadly. The geographic range of the disease is broad, encompassing areas in Asia, Africa, South America, and the warmer regions of Europe and North America. It is estimated nearly 3 million people are infected by any manifestation of the disease each year and roughly a billion people live in endemic areas. Treatments for the disease are available, though demanding treatment regimens and high costs can be prohibitive for many. No vaccine is currently available, but previous exposure generally confers immunity against future exposures to the same species of Leishmania. The antiquated practice of leishmanization takes advantage of this. The process involves the administration of exudate from active CL lesions to an open wound on an individual to be immunized. It is believed this practice is still used in some areas. Given the fact parasites known to cause CL have considerable geographic overlap with those that cause VL it is possible for people in endemic areas to have exposures to both in their lifetime. This calls into question the disease outcomes for individuals that experience heterologous secondary exposure after recovering from earlier infection. Studies have addressed this question by using L. major as a primary infection followed by L. infantum challenge in the murine model. Results are contentious, with reports of heterologous protection against L. infantum and others reporting disease exacerbation. Observations of increased disease severity hint at the possibility of antibody dependent enhancement of infection (ADE). Herein we explore the possibility of extrinsic ADE as a result of heterologous exposure to L. major and L. infantum in vitro. ELISA was done to verify cross reactivity of L. major antiserum to antigen derived from both L. major and L. infantum. Results indicate substantial cross reactivity to the two antigens. This was followed with phagocytosis assays to measure parasite uptake by macrophages in vitro. J774 macrophages were combined with either L. major or L. infantum in the presence of L. major antiserum, naïve serum, or no serum. Parasite uptake was measured at several time points using flow cytometry. In the presence of L. major antiserum we observed significantly higher rates of L. major uptake but no effect on L. infantum uptake. Our results would suggest increased disease severity observed by others in vivo is not a result of extrinsic ADE. We hypothesize biased memory T cell responses, possibly as a result of intrinsic ADE caused by Fcγ signaling, could account for disease exacerbation in the animal model.