Transcriptomic and metagenomic characteristics of visceral leishmaniasis

Leishmaniasis can take several clinical forms, the most severe of which is visceral leishmaniasis (VL), the topic of this thesis. Traditionally called a tropical disease because of its prevalence in countries with warm climates and lower income populations, leishmaniasis is now recognized in many countries including high income nations in Europe and the USA. The parasites that usually cause VL are Leishmania donovani and L. infantum. An oddity of leishmaniasis is the fact that infection can either be controlled by the host immune response and never become symptomatic, or it can lead to progressive infection that in the case of VL is usually fatal if untreated. This thesis is focused on discovering immune mechanism that underlie the ability of a human host to mount an effective immune response and prevent or cure symptomatic infection. We did this through RNA sequencing of two important classes of immune cells that determine whether cure occurs: CD4+ T-cells, and monocytes/microphages that express CD14 on their surface. Our studies were focused on patients with VL in India where the disease has taken a tremendous toll over the past decades. The transcriptomes of CD4+ and CD14+ cells from blood and bone marrow were compared to those of people from the same endemic region of India who did not have leishmaniasis. Our studies led us to insights into the immune factors active during VL, and the fact that abundant L. donovani parasites inhabit the blood and bone marrow of these individuals. The recent SARS-CoV-2 pandemic has taught us that the global sharing of resources and products is accompanied by the global sharing of infectious diseases. Thus, it is important to study diseases such as leishmaniasis, which are endemic in many low-income nations but are now spilling over into high income nations. Practicing compassion for those with diseases of poverty will eventually help an even larger portion of society.