Phagocytes and the Leishmania Parasite: A Marriage of Convenience

ABSTRACT

The current drive by the Government of India to eliminate Leishmaniasis has pinpointed post-kala azar dermal leishmaniasis (PKDL) as the strongest contender for the disease reservoir. This emphasizes the necessity to consider the eradication of PKDL as top priority, and hinges on its early diagnosis and management. We undertook this challenge and have provided insights into Leishmania biology, by focusing our efforts in (i) delineating the immunopathogenesis of PKDL, a disease unique to South Asia (ii) developing diagnostic/prognostic tools for monitoring antileishmanial treatment in patients with visceral leishmaniasis and PKDL. In order to delineate the immunopathogenesis of PKDL, it was established that the parasite adopts multiple approaches to deviously manipulate host monocytes/macrophages, and thus facilitate parasite survival and disease progression. The parasite adopts a multipronged approach that includes attenuation of the oxidative burst within phagocytes, polarization of monocytes/ macrophages towards alternate activation, enhancement of CD8 T-cell exhaustion and a decreased presence of Langerhans cells. Identification of these immunological changes have allowed for development of biomarkers that have been exploited to develop diagnostic and prognostic markers for monitoring the disease progression, either in terms of antibody based markers, or quantification of the parasite load, the latter being the most definitive approach. Measurement of parasite load has proved to be an effective tool for monitoring the effectiveness of chemotherapy. Taken together, the identification of biomarkers and new chemotherapeutic modalities has helped in improved management and potential elimination of leishmaniasis.