Fig 2: Expression of IL-1 pathway genes are upregulated in MPN.a Expression of IL-1R pathway gene signatures is tested for enrichment by Gene Set Enrichment Analysis (GSEA) in peripheral blood CD34+ HSPCs from PMF patients (n = 23) and bone marrow CD34+ HSPCs from normal controls (n = 15). Comparisons with p-value <0.05 and FDR q-value <0.05 were considered significant. Analysis of publicly available dataset19. Affymetrix data were dowloaded as normalized expression levels from Gene Expression Omnibus database (GSE53482)19 using the GEOquery package (R, Vienna, Austria. https://www.R-project.org/). The normalization of the expression data was checked by boxplot representation. Gene Set Enrichment Analysis (GSEA) was performed with the GSEAv4.1.0 software (Broad Institute). All gene sets were obtained from GSEA website (https://www.gsea-msigdb.org). Enrichment map was used for visualization of the GSEA results. Normalized Enrichment score (NES) and False discovery rate (FDR) p-values were applied after a 10,000 gene set permutations. b Heatmap representation of expression levels of IL-1R pathway genes in CD34+ HSPCs from PMF patients (n = 23) and normal controls (n = 15). Analysis of publicly available dataset19. c Heatmap representation of the differential expression of IL-1 signaling pathway genes in hematopoietic stem cells (HSC; Lin-Sca1+cKit+CD48-CD150+), megakaryocyte-erythroid precursors (MEP or pre-MegE; Lin-Sca1-cKit+CD41-CD16-105-CD150+) and megakaryocyte progenitors (MkP; Lin-Sca1-cKit+CD41+CD150+) between VF (n = 3) and WT (n = 3) mice is shown (left). Barcode plots showing custom Gene Set Enrichment Analysis (GSEA) of the Biocarta IL-1R pathway in HSC, pre-MegE (or MEP) and MkP from VF vs WT (right). Source data are provided as a Source Data file.

Fig 3: EphA2 Is Required for Maximal Fungal Killing of Serum-Opsonized Yeast-Phase C. albicans(A) Killing of serum-opsonized yeast-phase C. albicans by peripheral blood (PB) and bone marrow (BM) neutrophils isolated from wild-type and EphA2-/- mice. The percentage of organisms killed was determined by colony counting. Results are means ± SD from 4 experiments, each performed in triplicate. ****p < 0.0001 (Mann-Whitney test).(B) Killing of unopsonized C. albicans yeast by neutrophils from the indicate mouse strains. NS, not significant.(C) Neutrophil killing of opsonized C. albicans hyphae.(D) Killing of serum-opsonized yeast-phase C. albicans by bone marrow-derived macrophages.(E) Killing of opsonized yeast C. albicans by a mixed wild-type and EphA2-/- population. Results are means ± SD from 3 independent experiments, each performed in duplicate. ***p < 0.001; ****p < 0.0001 (Mann-Whitney test corrected for multiple comparisons).(F) Phagocytosis of opsonized C. albicans yeast by wild-type and EphA2-/- neutrophils. NS, not significant. Data were normalized to the phagocytosis of wild-type neutrophils.(G) Neutrophil killing of serum-opsonized S. aureus.(H) Body weight of wild-type and EphA2-/- mice after oral infection with C. albicans. Results are median ± interquartile range of 5 mice per strain in a single experiment. *p < 0.05 (Mann-Whitney test for each day).(I) Oral fungal burden of wild-type and EphA2-/- mice after 4 days of OPC. Results are median ± interquartile range of five mice per group in a single experiment. **p < 0.01 (Mann-Whitney test). The y axis is set at the limit of detection (20 CFUs per gram of tissue).(J) Fc?R signaling is required for killing of serum-opsonized C. albicans yeast. The neutrophil Fc?Rs, CD16, CD32, and CD64 were blocked using specific Abs, after which the killing of serum-opsonized yeast-phase C. albicans was determined by colony counting. Results are means ± SD from 4 experiments in triplicate. ****p < 0.0001, NS, not significant (Mann-Whitney test).(K) Fc?R signaling is required for yeast phagocytosis. The neutrophil Fc?Rs, CD16, CD32, and CD64 were blocked using specific Abs, after which phagocytosis of opsonized C. albicans yeast by wild-type was determined. Results are means ± SD from 3 independent experiments, each performed in duplicate. **p < 0.01 (Mann- Whitney test).(L) Oral fungal burden of wild-type and FcyRI-/- mice after 2 days of OPC. Results are median ± interquartile range of five mice per group in a single experiment. **p < 0.01 (Mann-Whitney test). The y axis is set at the limit of detection.See also Figure S4.