Functional Immunophenotyping for Precision Therapies in Sepsis.

Sepsis remains a significant cause of morbidity and mortality worldwide. While many more patients are surviving the acute event, a substantial number enter a state of persistent inflammation and immunosuppression, rendering them more vulnerable to infections. Modulating the host immune response has been a focus of sepsis research for the past fifty years, yet novel therapies have been few and far between.

Surviving septic patients endotyped with a functional assay demonstrate active immune responses.

Introduction: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.

Development and optimization of a diluted whole blood ELISpot assay to test immune function.

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis ('SPIES') is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay.

Protocol for inducing monomicrobial sepsis in mice with uropathogenic E. coli.

Bacterial infections are the primary cause of pathogenic sepsis. An uropathogenic E. coli (UPEC) model of monomicrobial sepsis represents a useful tool for interrogating the host immune response to this pathogen.

Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8 T cells revealed by intravital imaging.

Lung-tissue-resident memory (T) CD8 T cells are critical for heterosubtypic immunity against influenza virus (IAV) reinfection. How T cells surveil the lung, respond to infection, and interact with other cells remains unresolved. Here, we used IAV infection of mice in combination with intravital and static imaging to define the spatiotemporal dynamics of lung T cells before and after recall infection.