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. Author manuscript; available in PMC: 2016 Sep 10.
Published in final edited form as: Cell. 2015 Sep 3;162(6):1309–1321. doi: 10.1016/j.cell.2015.08.027

Figure 4. Heterogeneity of the invading bacterial populations shapes a heterogeneous host Type I IFN response.

Figure 4

(A) Schematic of iBMMs with a transcriptional reporter (6XISRE-GFP) of the activity of the Type I IFN gene cluster. (B). Shown is an MA plot of the induction levels of host and bacterial transcripts in ISRE-positive over ISRE-negative cells (y-axis) versus average absolute read counts (x-axis). Infected ISRE- positive cells expressing high levels of Cluster III genes (green dots) are infected with bacteria expressing higher levels of PhoP regulated genes (red dots) compared with ISRE-negative cells. Inset indicates the enrichment of PhoPQ regulated genes and Cluster III (GSEA analysis, p=0.007 and p<0.001 respectively). (C) Schematic of S. typhimurium with the transcriptional reporter of PhoP activity (phoP-GFP, top). PhoP displayed bimodal activity in infected macrophages, as analyzed by FACS (bottom, infected cells were identified by pHrodo). (D) Cells infected with bacteria expressing high phoP-GFP show higher expression of Cluster III genes compared to cells infected with low phoP-GFP. (E) Plots summarize the expression of the Type I IFN response in BMMs infected with WT, PhoP–, or PhoPc strains of S. typhimurium with a weighted average based score (x-axis) and display it versus the frequency of single cells (y-axis). Infection with PhoPc results in induction of the Type I IFN response in almost all infected cells, compared to cells infected with WT or PhoP– strains. (Table S4)