Deconvolution of Bulk Transcriptomics Data Suggests Changes in Conjunctival Immune Cell Populations in Trachoma

Abstract

Abstract Objective: Trachoma, a neglected tropical disease caused by ocular infection with Chlamydia trachomatis, progresses from repeated infections and conjunctivitis to scarring, trichiasis and blindness. It is yet unknown which immune cells are responsible for mediating pathogenesis. Our objective was to deconvolute bulk transcriptomics data in order to estimate how conjunctival immune cell populations change in active and scarring trachoma. Results: Six deconvolution methods (quanTIseq, TIMER, MCP-counter, xCell, EPIC, and CIBERSORT) were used to estimate the relative abundance of cell populations in five bulk transcriptomic datasets. Cell types from each deconvolution method were mapped to one another using the Immunedeconv R package. In active disease, B cells, neutrophils, natural killer cells, CD4+ T cells and CD8+ T cells were raised (direction of change the same for at least 75% of methods, p<0.05 for at least two methods by logistic regression). B cells and neutrophils were raised in trachomatous scarring and inflammation, while the relative abundance of CD8+ T cells was decreased. In those with scarring and no inflammation, monocyte/macrophages, neutrophils and CD8+ T cells were decreased compared with controls.