Single-cell analysis of mouse microglia carrying the mouse Nlrp3 wildtype locus, the human NLRP3 wildtype knock-in or the human NLRP3 D305N variant knock-in gene.

We used single cell RNA-sequencing to characterize the immune cell population of CD45+ cells in the brains of these mice, compared to hNLRP3_WT and mNlrp3_WT controls. We identified elevated peripheral immune cell populations in hNLRP3_D305N, with neutrophils, T cells, and monocytes as the most prevalent populations. hNLRP3_D305N microglia also showed broad transcriptional shifts towards more reactive profiles and the emergence of distinct subpopulations that were also defined by expression of proinflammatory genes.