Mitali Chatterjee’s research work embodies ‘Translational research in Indian leishmaniasis’ (visceral and post-kala-azar dermal Leishmaniasis), which includes delineating disease-specific biomarkers and exploiting their specificity for improved diagnosis, identification of factors contributing to antimonial unresponsiveness and evaluation of newer chemotherapeutic modalities for better management of leishmaniasis. She was elected Fellow of the Indian Academy of Sciences in 2017.
Session 1E: Inaugural Lectures by Fellows
Leishmania donovani is the causative organism of acute visceral leishmaniasis (VL) and its chronic dermal sequel, post-kala-azar dermal leishmaniasis (PKDL). In South Asia, where the transmission of VL is anthroponotic, patients with PKDL are the proposed disease reservoir and its eradication is linked to the control of leishmaniasis, thus emphasizing its epidemiological relevance. In the absence of an animal model and its low incidence, factors contributing towards the immunopathogenesis of PKDL have remained an open-ended, yet pertinent question, and these are precisely the challenge that the speaker’s group undertook. The survival of the Leishmania parasite within monocytes/macrophages hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, they aimed to delineate this biological niche in patients with PKDL.Within monocytes, the parasite attenuated generation of an oxidative burst, lowered the expression of toll-like receptors (TLR4), concomitant with a pronounced impairment of antigen presentation and co-stimulation, evident by down-regulation of CD54, HLA-DR and CD86. The monocytes/macrophages displayed polarization towards an alternatively activated phenotype with a consistent increase in expression of classical M2 markers. Additionally, dendritic cells (DC), the major sentinels of host defence of the immune response and critical for antigen presentation were significantly decreased. Another key change was the conspicuous absence of CD4+ Tcells, concomitant with an enhanced infiltration of CD8+ T-cells, which demonstrated an absence of perforin, granzyme and Zap-70. Additionally, these dermal lesions showed an enhanced expression of PD-1 and the skin-homing chemokine CCL17, which suggested dermal homing of CD8+ T-cells that underwent exhaustion. Taken together, the homing of anergic/exhausted CD8+ T-cells enhanced presence of alternatively activated macrophages and a decreased expression of dendritic cells collectively facilitated establishment of an immunosuppressive milieu that supported parasite survival and disease progression.