| Source . | Inflammatory pathway . | Molecular mechanism . | Effect on HSCs . | Reference . |
|---|---|---|---|---|
| Viral | ||||
| Lymphocytic choriomeningitis virus | IFN-α/β–IFNAR | ND | 30-fold reduction on CFU (at infection day 3) | Binder et al. (1997) |
| IFN-γ–IFNGR | IFN-γ–induced SOCS1 inhibits TPO-induced STAT5 phosphorylation and leads to decreased/increased cyclin D1/Cdkn1C | Decreased pool recovery and self-renewal capacity (at infection days 4–12) | de Bruin et al. (2013) | |
| IFN-γ–IFNGR | IFN-γ–induced Cebpb in high IFNGR–expressing myeloid-biased HSCs | Increased proliferation and myeloid bias associated to decreased self-renewal (at infection day 6) | Matatall et al. (2014) | |
| IFN-γ–IFNGR–IL-6 | Cytotoxic CD8+ T cell–produced IFN-γ activates IL-6 production by BM MSCs, leading to reduced Runx-1 and Cebpa expression | Increased myeloid-differentiation bias on HSPCs | Schürch et al. (2014) | |
| IFN-α/β–IFNAR and IFN-γ–IFNGR | Persistent destruction of CARc networks by virus-specific IFN-producing CD8+ T cells—loss of HSC quiescence–enforcing niche | Increased proliferation, decreased pool size, and decreased repopulating capacity | Isringhausen et al., 2020 Preprint | |
| Murine cytomegalovirus | Increased IFN-γ, IL-17, and CCL12 levels | Inflammatory milieu associates in an IFNAR-independent manner with increased Sca-1 and Evi1 gene expression in HSCs | Decreased repopulating capacity and increased myeloid differentiation, after BM viral clearance (at infection day 21) | Hirche et al. (2017) |
| Bacterial | ||||
| Polymicrobial sepsis using cecal ligation and puncture model | ND | HSC expansion associates with reduced BM cellularity but is independent from MyD88, TRIFF, IFNAR, TNF-α, IL-1, IL-6, prostaglandins, oxidative stress, and super antigen signaling | Increased pool size | Scumpia et al. (2010) |
| Escherichia coli | G-CSF/CXCL12 | Dual stimulation of NOD1 and TLR4 leads to increased G-CSF and decreased CXCL12 production in radioresistant endothelial cells | Increased mobilization of BM-expanded HSCs, reduced repopulating capacity, and increased myeloid-differentiation | Burberry et al. (2014) |
| SHH-GLI | ERK1/2–SP1–mediated increased SHH expression in Lin+ BM cells leads to higher GLI levels in HSCs | Proliferation and myeloid differentiation | Shi et al. (2018) | |
| IFN-γ–IFNGR | ND | Increased proliferation and decreased repopulating capacity (4 wk after single bacterial inoculation) | Baldridge et al. (2010) | |
| M. avium | IFN-γ–IFNGR | IFN-γ–induced Batf2 leading to HSPC terminal differentiation | Decreased pool size, repopulating capacity, and increased myeloid differentiation (after six monthly inoculations) | Matatall et al. (2016) |
| IFN-γ–IFNGR | IFN-γ–induced expression of BST2 (noncanonical E-selectin ligand) displaces HSCs from quiescence-enforcing CARc niche to an activating E-selectin–positive vascular niche | Increased proliferation, terminal differentiation, and decreased pool size (after four monthly inoculations) | Florez et al. (2020) | |
| Mycobacterium tuberculosis | TNF-α/IL-6 | TLR2 and MyD88 bacterial sensing dependent | Increased HSPC pool and myeloid differentiation | Choi et al. (2011) |
| IFN-α/β–IFNAR | IFNAR-dependent reprogramming of HSCs leading to dysregulated iron metabolism, depolarized mitochondrial membrane, and necrosis in myeloid progenitors | Decreased pool and reconstitution capacity (up to 1 yr after infection) | Khan et al. (2020) | |
| Ehrlichia muris | IFN-γ–IFNGR | ND | Decreased pool and reconstitution capacity, and increased myeloid differentiation bias (at infection day 8) | MacNamara et al. (2011) |
| IFN-α/β–IFNAR | Direct sensitization of HSPCs to RIPK1-dependent death and increased HSC proliferative arrest | Decreased pool and reconstitution capacity (at infection day 7) | Smith et al. (2018) | |
| Protozoan | ||||
| Plasmodium berghei | ND | ND | Increased proliferation and pool size (at infection days 7–10) | Vainieri et al. (2016) |
| IFN-γ–IFNGR | Loss of BM niche osteoblasts and endothelial cell properties | Increased turnover leading to decreased functionality and transcriptional identity | Haltalli et al. (2020) | |
| Fungal | ||||
| Candida albicans | ND (TNF-α?) | TLR2/MyD88 and dectin-1 fungal sensing dependent | Increased proliferation and pool size | Martínez et al. (2018) |
| IL-1β and GM-CSF/CD131 | β-glucan–mediated IL-1β and GM-CSF production by BM cells leads to increased glycolytic pathways and proliferation in HSCs | Increased proliferation, pool size, and myeloid differentiation bias (at 7 d after exposure) | Mitroulis et al. (2018) |
| Source . | Inflammatory pathway . | Molecular mechanism . | Effect on HSCs . | Reference . |
|---|---|---|---|---|
| Viral | ||||
| Lymphocytic choriomeningitis virus | IFN-α/β–IFNAR | ND | 30-fold reduction on CFU (at infection day 3) | Binder et al. (1997) |
| IFN-γ–IFNGR | IFN-γ–induced SOCS1 inhibits TPO-induced STAT5 phosphorylation and leads to decreased/increased cyclin D1/Cdkn1C | Decreased pool recovery and self-renewal capacity (at infection days 4–12) | de Bruin et al. (2013) | |
| IFN-γ–IFNGR | IFN-γ–induced Cebpb in high IFNGR–expressing myeloid-biased HSCs | Increased proliferation and myeloid bias associated to decreased self-renewal (at infection day 6) | Matatall et al. (2014) | |
| IFN-γ–IFNGR–IL-6 | Cytotoxic CD8+ T cell–produced IFN-γ activates IL-6 production by BM MSCs, leading to reduced Runx-1 and Cebpa expression | Increased myeloid-differentiation bias on HSPCs | Schürch et al. (2014) | |
| IFN-α/β–IFNAR and IFN-γ–IFNGR | Persistent destruction of CARc networks by virus-specific IFN-producing CD8+ T cells—loss of HSC quiescence–enforcing niche | Increased proliferation, decreased pool size, and decreased repopulating capacity | Isringhausen et al., 2020 Preprint | |
| Murine cytomegalovirus | Increased IFN-γ, IL-17, and CCL12 levels | Inflammatory milieu associates in an IFNAR-independent manner with increased Sca-1 and Evi1 gene expression in HSCs | Decreased repopulating capacity and increased myeloid differentiation, after BM viral clearance (at infection day 21) | Hirche et al. (2017) |
| Bacterial | ||||
| Polymicrobial sepsis using cecal ligation and puncture model | ND | HSC expansion associates with reduced BM cellularity but is independent from MyD88, TRIFF, IFNAR, TNF-α, IL-1, IL-6, prostaglandins, oxidative stress, and super antigen signaling | Increased pool size | Scumpia et al. (2010) |
| Escherichia coli | G-CSF/CXCL12 | Dual stimulation of NOD1 and TLR4 leads to increased G-CSF and decreased CXCL12 production in radioresistant endothelial cells | Increased mobilization of BM-expanded HSCs, reduced repopulating capacity, and increased myeloid-differentiation | Burberry et al. (2014) |
| SHH-GLI | ERK1/2–SP1–mediated increased SHH expression in Lin+ BM cells leads to higher GLI levels in HSCs | Proliferation and myeloid differentiation | Shi et al. (2018) | |
| IFN-γ–IFNGR | ND | Increased proliferation and decreased repopulating capacity (4 wk after single bacterial inoculation) | Baldridge et al. (2010) | |
| M. avium | IFN-γ–IFNGR | IFN-γ–induced Batf2 leading to HSPC terminal differentiation | Decreased pool size, repopulating capacity, and increased myeloid differentiation (after six monthly inoculations) | Matatall et al. (2016) |
| IFN-γ–IFNGR | IFN-γ–induced expression of BST2 (noncanonical E-selectin ligand) displaces HSCs from quiescence-enforcing CARc niche to an activating E-selectin–positive vascular niche | Increased proliferation, terminal differentiation, and decreased pool size (after four monthly inoculations) | Florez et al. (2020) | |
| Mycobacterium tuberculosis | TNF-α/IL-6 | TLR2 and MyD88 bacterial sensing dependent | Increased HSPC pool and myeloid differentiation | Choi et al. (2011) |
| IFN-α/β–IFNAR | IFNAR-dependent reprogramming of HSCs leading to dysregulated iron metabolism, depolarized mitochondrial membrane, and necrosis in myeloid progenitors | Decreased pool and reconstitution capacity (up to 1 yr after infection) | Khan et al. (2020) | |
| Ehrlichia muris | IFN-γ–IFNGR | ND | Decreased pool and reconstitution capacity, and increased myeloid differentiation bias (at infection day 8) | MacNamara et al. (2011) |
| IFN-α/β–IFNAR | Direct sensitization of HSPCs to RIPK1-dependent death and increased HSC proliferative arrest | Decreased pool and reconstitution capacity (at infection day 7) | Smith et al. (2018) | |
| Protozoan | ||||
| Plasmodium berghei | ND | ND | Increased proliferation and pool size (at infection days 7–10) | Vainieri et al. (2016) |
| IFN-γ–IFNGR | Loss of BM niche osteoblasts and endothelial cell properties | Increased turnover leading to decreased functionality and transcriptional identity | Haltalli et al. (2020) | |
| Fungal | ||||
| Candida albicans | ND (TNF-α?) | TLR2/MyD88 and dectin-1 fungal sensing dependent | Increased proliferation and pool size | Martínez et al. (2018) |
| IL-1β and GM-CSF/CD131 | β-glucan–mediated IL-1β and GM-CSF production by BM cells leads to increased glycolytic pathways and proliferation in HSCs | Increased proliferation, pool size, and myeloid differentiation bias (at 7 d after exposure) | Mitroulis et al. (2018) |