葡萄球菌肠毒素 B 诱导的急性呼吸窘迫综合征中巨噬细胞的异质性.pdf

1、Heterogeneity of macrophages in Staphylococcal Enterotoxin B induced Acute Respiratory Distress SyndromeKiesha Wilson,PhDAssistant ProfessorDepartment of Pathology,Microbiology,&ImmunologyAcute Respiratory Distress Syndrome(ARDS)Acute Respiratory Distress Syndrome(ARDS)Cytokine storm Fluid build Epi

2、demiology 30-40%mortality based on severity of disease.No Cure Treatment includes:Ventilation,Oxygen Support,and Fluid Management.Matthay et al(2019)Staphylococcus Enterotoxin B(SEB)Staphylococcal Enterotoxin B(SEB)Superantigenic region of SEB similar to SARS-CoV-2 spike protein motif(Function Diffe

3、rs)Superantigen sAG binds to MHC and activates T-cells Toxic Shock Syndrome,Food Poisoning,ARDS,Sepsis BiowarfareCheng et al(2021)SuperantigenConventionalAntigenAntigen Binding CleftPROJECT OVERVIEWSEB-induced ARDS is fatal in C3H/HeJmice when given as a dual dose within 7 days Tissues collected 72

4、hours post-toxin introduction Single Cell RNA-seq and Single Cell ATAC-seq performed on whole lung single cell suspension5g Intranasal2g Intraperitoneal2 Hours5-7 DaysMacrophage Differentiation Monocyte/Macrophage Differentiation Bone Marrow Derived CD14+,CD14+/CD16+,CD16+APC Alveolar and Interstiti

5、al Macrophages SiglecF+,CD11c+,CD11b-Cx3cr1+,CD11b+,CD64 Martinez et.Al(2020)Single Cell RNA Seq SEB causes Increased chromatin accessibility of IFSG in myeloid cells MacrophagesIncreased chromatin accessibility Stat1 and Irf9 critical regulators of severe COVID-19 associated ARDSIrf9Stat1scRNA-seq

6、shows SEB increases myeloid cellsscRNA-seqshows SEB increases myeloid cellsSEB+VEHNaive+VEHCell Distribution%NaveSEBMafb Mac2.1724.02Memory B22.384.61Memory T11.3112.14Neutrophils1.6314.53Alveolar Macrophage15.364.17Activated T12.123.78Ifitm6 Mac1.2210.68PM7.911.96CD8 Proliferating T0.898.94NK6.062.