Fig. 5: Transcriptomic signatures of adaption and degranulation activity in NK cells from LN during SIVagm infection.

a Venn diagrams generated by the intersection of the list of up- and down-regulated genes with an adjusted p-value < 0.05 based on the genome-wide transcriptome. b The pie chart shows the enriched Gene Ontology (GO) terms for the 176 genes that were upregulated in NKG2_a/c^low and CXCR5⁺ NK cell subsets as compared to NKG2_a/c^highCD16⁻ NK cells. The mRNAs were input for ClueGO plugged into Cytoscape for GO enrichment analysis. The ‘cellular component’, ‘biological process’, ‘molecular function’, and ‘immune system process’ GO terms were selected for this analysis. The two-sided hypergeometric test was used in the statistical inference. The term value corrected with the Bonferroni step down method was applied for p-value correlation. The adjusted p-value threshold was set to 0.001. The list of the associated genes found for each GO term is given in Supplementary Table S4. c Volcano plots that represent up- and down-regulated transcripts of each of the three NK cell subsets when compared to NKG2_a/c^highCD16⁻ NK cells. The size of each data point is calculated as −log10 (p-value) × log2 (FC), with a p-value cutoff <0.05. The red dots represent the 30 highest upregulated transcripts in NKG2_a/c^lowCD16⁺ versus NKG2_a/c^highCD16^- NK cells. These transcripts were then highlighted on the volcano plots obtained for the two other comparisons. The blue dots represent the transcript coding for CCDC102B, which was downregulated in all three comparisons. On the graph the name of some proteins corresponding to a given transcript are provided. The list of all transcripts upregulated for each comparison is given in the Data Source file. d, e Genome-wide transcriptomes were used to define heatmaps of d markers linked to ITAM/ITIM signaling pathways and e genes strongly upregulated in NKG2_a/c^lowCD16⁺ NK cells. The orange and blue colors indicate higher and lower levels of transcripts measured in LN NK cell subsets from three chronically infected monkeys. A p-value adjustment was performed to account for multiple comparisons and control the false positive rate to a chosen level. P values ≤ 0.05 were considered statistically significant. In panel d, e the gene and the name of the proteins corresponding to the transcripts are indicated. Source data been deposited in the Gene Expression Omnibus database; the accession number is GSE140600. f Spearman’s correlation between THEMIS and KLRC1 (NKG2A; r = −0.58, p = 0.0025, n = 24) or GRAP2 (r = 0.84, p < 0.000, n = 24) gene expressions. Each dot represents a NK cell subset from an individual animal. Dot circle represents the tissue from which NK cells were isolated.