# Enhanced resistance to Listeria infection in mice surviving sepsis: the role of lipid metabolism and myeloid cell reprogramming

## TL;DR

Mice that survive sepsis show improved resistance to Listeria infection due to changes in lipid metabolism and myeloid cell reprogramming.

## Contribution

The study reveals lipid metabolic reprogramming in myeloid cells as a novel mechanism for enhanced immunity in sepsis survivors.

## Key findings

- Sepsis survivors showed increased resistance to Listeria infection.
- Myeloid cells in sepsis survivors exhibited transcriptional reprogramming and lipid droplet accumulation.
- Systemic lipid remodeling was observed, with changes in phospholipid levels.

## Abstract

Immune resilience is the capacity of the immune system to recover from sepsis-induced organ injury and reestablish host defense. While sepsis survivors are often viewed as immunocompromised, recent studies suggest that some may acquire adaptive immune traits that enhance resistance to secondary infections.

We employed a murine cecal ligation and puncture (CLP) model to study polymicrobial sepsis and subsequent immune responses. Listeria monocytogenes was used as a model intracellular pathogen to assess immune protection. We analyzed myeloid cell phenotypes using single-cell RNA sequencing and evaluated lipid metabolic changes through quantitative RT-PCR, immunohistochemistry, serum cytokine assays, and plasma lipidomics.

Sepsis-surviving mice showed enhanced resistance to Listeria infection. Single-cell RNA sequencing revealed transcriptional reprogramming in splenic CD11b+Ly6Chigh myeloid cells, including downregulation of lipoprotein lipase and lipid efflux genes. CD11b+ myeloid cells exhibited increased lipid droplet accumulation, accompanied by elevated serum interferon-gamma (IFN-γ) levels. Plasma lipidomics identified systemic lipid remodeling, with increased phosphatidylserine and decreased phosphatidylinositol and phosphatidylglycerol levels.

Our findings suggest that sepsis survival induces lipid metabolic reprogramming in myeloid cells, contributing to enhanced immunity against intracellular pathogens. These insights reveal potential therapeutic targets within lipid metabolic pathways to improve host defense in sepsis survivors.