University Of Tasmania

File(s) under permanent embargo

Absence of TNF leads to alternative activation in peritoneal macrophages in experimental listeria monocytogenes infection

journal contribution
posted on 2023-05-21, 03:09 authored by Li, X, Chen, C, Zhang, L, Cheng, X, Geng, H, Ji, Q, Li, C, Chen, H, Heinrich KornerHeinrich Korner, Liu, X
Macrophages are crucial effectors of innate immunity against the pathogenic bacterium Listeria monocytogenes. The pro-inflammatory cytokine tumour necrosis factor-α (TNF) has been shown to be crucial for resistance to L. monocytogenes and mice deficient in TNF signalling succumb quickly after infection. However, the mechanisms underlying TNF-mediated defence against L. monocytogenes infection have not been completely elucidated. Here, we demonstrate that TNF concurrently functions to support a pro-inflammatory M1 phenotype while actively blocking macrophage polarization to the M2 phenotype. Compared to WT mice, peritoneal macrophages in TNF-deficient mice inoculated with L. monocytogenes respond with M2 polarization by upregulating Arg1. Consistently, TNF blockade in vitro resulted in M2 polarization in peritoneal macrophages during L. monocytogenes infection. Additionally, TNF promotes the transition from M2 to M1 polarization in peritoneal macrophages. Further investigation of peritoneal macrophage polarization suggested the NF-κB pathway is involved in the TNF-dependent M2 to M1 shift. Conversely, treatment of peritoneal macrophage with a PPARγ agonist blunted the expression of M1 genes induced by TNF and reduced NF-κB signalling pathway activation. Competing signalling mechanisms therefore play an essential role in the ability of peritoneal macrophage to resolve L. monocytogenes infections with TNF playing an essential role in driving M1 polarization.


Publication title

Immunological Investigations






Menzies Institute for Medical Research


Informa Healthcare

Place of publication

United Kingdom

Rights statement

Copyright 2021 Taylor & Francis Group

Repository Status

  • Restricted

Socio-economic Objectives

Diagnosis of human diseases and conditions

Usage metrics

    University Of Tasmania