Rajiv Kumar Poster 2023

Dr Rajiv Kumar

Banaras Hindu University India, India

Distinct CD4 + T Cells Immunological Signature in Patients with Post Kala-Azar Dermal Leishmaniasis

Poster Abstract

Post kala-azar leishmaniasis (PKDL), which is a late cutaneous manifestation of visceral leishmaniasis (VL), represents an important but largely neglected reservoir of infection and is considered as an important source for transmission of the disease. In efforts to eliminate VL, we also need to understand how parasites and the immune system interact to reconcile, how the disease is controlled and immunity develops in PKDL patients. CD4+ T cells play crucial roles in coordinating immune responses by producing molecules critical for the production of high-affinity antibodies B cells, essential for activation of CD8+ T cells to kill infected and transformed cells, as well as helping innate immune cells recognize and control pathogens. In this study, we examine the transcriptional signature of CD4+ T cells that could distinguish PKDL patients from endemic controls and visceral leishmaniasis (VL) patients. Blood samples were collected from clinically confirmed PKDL and VL patients as well as healthy endemic control (HEC) individuals to isolate PBMCs and enrich CD4+ T cells. RNA was isolated, libraries were prepared and RNA-sequence was employed to identify differentially expressed genes. 

We observed a number of differentially expressed genes (DEGs) unique to PKDL including CD68, IL-13RA, Galectin-2 (LGALS2), De Receptor-6/TNFRSF21 (which activates JNK and NF-κβ pathway), CCR1 as well as CXCR1 and CXCR2. NLRP-3 inflammasome as well as skin homing markers CCR4, CCR8 and CCR10 we also differentially upregulated in PKDL While notable downregulated DEGs in CD4+ T cells for PKDL compared to VL patients were LAG3 and IL-10, both with important functional roles in VL. Most importantly, NLRP-3 inflammasome and transcription factors EGR-1/2 distinguished nodular PKDL from macular PKDL. In summary, CD4+ T cells from PKDL patients have unique gene signatures which differentiate them from VL patients and HEC. Our results also showed the canonical NLRP3 inflammasome function is not confined to innate immune cells but is operative in adaptive CD4+ T cells.

Biography

Dr. Rajiv Kumar is an Assistant Professor (early career researcher) at Institute of Medical Sciences, Banaras Hindu University, Varanasi-India. His research interests are to understand the immune mechanisms underlying the progression of diseases such as Malaria and Visceral Leishmaniasis, and to distinguish anti-parasitic host immune responses that control disease from the responses that cause disease. He has a broad background in cellular and molecular immunology of infectious diseases, as well as significant field and epidemiological work experience.  He received training at NIAID, NIH in Bethesda, USA and at QIMR Berghofer Medical Research Institute, Brisbane, Australia. Dr. Kumar has established collaboration with QIMR Berghofer-Australia, Karolinska Institute -Sweden and University of Iowa-USA. He has published paper in prestigious international Journals like Nature Immunology, Cell Reports, Nature Medicine, PLoS Pathogens, Journal of Immunology, Journal of Infectious Diseases etc and his lab is funded by many national and international grants.