Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections

Abstract

Since the discovery of cell apoptosis, other gene-regulated cell deaths are gradually appreciated, including pyroptosis, ferroptosis, and necroptosis. Necroptosis is, so far, one of the best-characterized regulated necrosis. In response to diverse stimuli (death receptor or toll-like receptor stimulation, pathogenic infection, or other factors), necroptosis is initiated and precisely regulated by the receptor-interacting protein kinase 3 (RIPK3) with the involvement of its partners (RIPK1, TRIF, DAI, or others), ultimately leading to the activation of its downstream substrate, mixed lineage kinase domain-like (MLKL). Necroptosis plays a significant role in the host’s defense against pathogenic infections. Although much has been recognized regarding modulatory mechanisms of necroptosis during pathogenic infection, the exact role of necroptosis at different stages of infectious diseases is still being unveiled, e.g., how and when pathogens utilize or evade necroptosis to facilitate their invasion and how hosts manipulate necroptosis to counteract these detrimental effects brought by pathogenic infections and further eliminate the encroaching pathogens. In this review, we summarize and discuss the recent progress in the role of necroptosis during a series of viral, bacterial, and parasitic infections with zoonotic potentials, aiming to provide references and directions for the prevention and control of infectious diseases of both human and animals.

Myeloid PTEN controls STING-induced inflammation and necroptosis through NCID/NRF2 signaling in APAP-induced liver injury

“…The generation of ROS instigates necroptosis, a cellular process that necessitates the participation of RIPK3 and its substrate MLKL. RIPK3 activation, which is controlled by caspase-mediated cleavage and serves as a crucial switch for necroptosis and in ammation, enhanced in ammation-related cell death and damage in several in ammatory disease models [50] . Phosphorylation-mediated activation of MLKL causes it to move to the inner leaflet of the plasma membrane, disrupting cell integrity and prompting necroptosis [51] .…”

Progress on innate immune evasion and live attenuated vaccine of pseudorabies virus

“…Target Pathway Molecular mechanism References release a large number of damage-associated molecules and triggering an inflammatory response (Kaczmarek et al, 2013;Pasparakis and Vandenabeele, 2015;Zhang G. et al, 2022). PRV causes cell necroptosis in a RIPK3-dependent manner, and inhibition of necroptosis promotes PRV replication (Gou et al, 2021).…”

The Intersection between Bacterial Metabolism and Innate Immunity

“…Low fumarate concentrations and generation of mitochondrial ROS by keratinocytes lead to necroptosis, a form of programmed cell death characterized by inflammation and epithelial damage in the absence of significant recruitment of macrophages and neutrophils as seen in pyroptosis (Fig. 1) [53, 54]. The tissue damage and reduced recruitment of macrophages and neutrophils allow the internalization and passage of SCVs across the skin barrier [50].…”

“…Rather, it relies on the synthesis of branched-chain fatty acids to confer membrane fluidity and viability [90]. Lipoproteins are critical extracellular PAMPs derived from Gram-positive bacteria that are sensed through TLR2 [54]. S. aureus lipoproteins engage TLR2 receptors via esterified fatty acids, the composition of which could alter immunostimulatory capacity [93].…”