Absence of TNF Leads to Alternative Activation in Peritoneal Macrophages in Experimental Listeria Monocytogenes Infection

Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF

“…Our experiments were initiated with the idea of establishing the mechanistic basis of the anti-M2 effects of TNF; in part, we reasoned that as anti-TNF biologics have a vast spectrum of activities in RA and IBD patients, we should be able to elucidate a signaling framework that connects successful anti-TNF therapy with the number and function of M2 macrophages. In previous experimental systems, we and others showed that many hallmark M2 genes were negatively regulated by TNF (Kroner et al, 2014;Kratochvill et al, 2015b;Schleicher et al, 2016;Li et al, 2017Li et al, , 2021. Here, we used more general approaches to evaluate the global effects of TNF on M2 gene expression.…”

“…Recently, an additional and unexpected connection between TNF blockade and resolving inflammation was exposed using molecular genetic approaches. In mice lacking the type 1 tumor necrosis factor receptor (TNFR1, encoded by Tnfr1a) or TNF (encoded by Tnf), diverse inflammatory responses were associated with a striking enhancement of macrophages with M2 characteristics ( Kroner et al, 2014 ; Kratochvill et al, 2015b ; Schleicher et al, 2016 ; Li et al, 2017 , 2021 ). M2 macrophages (also referred to as alternatively activated macrophages) are enriched in inflammation associated with type 2 immune responses, IL4 and IL13 production, and transitions to wound healing and tissue repair.…”

Circadian Rhythms in Bacterial Sepsis Pathology: What We Know and What We Should Know

“…Nevertheless, in response to infectious or inflammatory stimuli, the cellular composition of the peritoneal cavity is altered ( Cassado Ados et al., 2015 ). Despite the relatively little information focused on the functional profile induced by stimulation of SPM and LPM cells, data showed that both cell types can differentiate into both M1 (classically activated, pro-inflammatory) and M2 (alternative activated, anti-inflammatory) cells depending on the stimuli ( Yuan et al., 2017 ; Li et al., 2021 ). Moreover, immune stimuli induce a decrease in LPMs levels, a phenomenon known as macrophage disappearance reaction [MDR ( Okabe and Medzhitov, 2014 )], which can include cell apoptosis ( Luan et al., 2015 ), local clot form ( Zhang et al., 2019 ) and migration ( Okabe and Medzhitov, 2014 ).…”