Caspases in Inflammation and Immunity

Abstract

Two of the main challenges that eukaryotic multicellular organisms faced during evolution were to cope with invading microorganisms and to eliminate infected cells. The immune system evolved to handle both tasks. Intertwined with immunity is programmed cell death that tailors the immune response and provides an effective way to remove infected cells. Caspases, effectors of inflammation and programmed cell death cascades, are perfectly suited to regulate the host response to invaders and injury. Their activity as inflammatory and killer proteases is regulated by direct binding to sensors of pathogens or danger, they can be modified following activation of signalling cascades by feedback mechanisms to terminate the inflammatory response and control cell survival, and they associate with coactivators and corepressors whose expression is closely linked to the needs of the cell. Key concepts Cell death and innate immunity are ancient evolutionarily conserved processes that utilize a number of related effectors and parallel signal transduction mechanisms. Innate immunity provides first line defences against pathogens and acts as a sentinel that primes adaptive immunity. Innate immunity depends on evolutionarily conserved germline‐encoded pattern recognition receptors (PRRs) that ‘sense’ pathogen‐associated molecular patterns (PAMPs) and ‘danger’ signals. The role of caspases in innate immunity is conserved through evolution. Caspase‐1, the prototypical member of the inflammatory caspase subfamily, contributes to host defence through different interrelated mechanisms, notably cell repair, inflammation and cell death. Caspase‐1 activity is necessary for host resistance to pathogens; however, when deregulated, it is at the basis of multiple inflammatory diseases. Inflammatory caspases are activated in NLR‐scaffolded multiprotein complexes termed ‘inflammasomes’ that are reminiscent of the apoptosome. Caspase‐12, an inflammatory caspase related to caspase‐1, is an endogenous inhibitor of the inflammasome. Apoptosis tailors adaptive immunity. Mutations in Casp‐8 and Casp‐10 cause autoimmune lymphoproliferative syndrome (ALPS). Excessive apoptotic caspase activity contributes to the pathogenesis of inflammatory diseases such as severe sepsis.

Apoptotic neurodegeneration in whitefly promotes the spread of TYLCV

“…In mammals, the sickness behavior is the result of neuroinflammation induced by activation of the innate immune system ( Godbout et al, 2005 ). The toll-like receptor (TLR) and nod-like receptor (NLR) cascades that are triggered by pathogens amplify the signal of several inflammatory programmed cell death formats in the central nervous system (CNS) ( Dantzer et al, 2008 ; Heneka et al, 2014 ; Heneka et al, 2018 ; LeBlanc and Saleh, 2009 ; Man et al, 2017 ). With the loss of neurons, the motor and sensory deficits become irreversible in the case of permanent tissue damage to the host of pathogens ( Glass et al, 2010 ; Shattuck and Muehlenbein, 2015 ).…”

Upregulation ofAtg5andAIFgene expression in synchronization with programmed cellular death events in integumental epithelium ofBombyx moriinduced by a dipteran parasitoid infection

“…Subsequent increase was noticed in the later stage of infection, at 120 h after infection. The initial rise in caspase expression is associated with cellular protection while the later enhancement is related with cellular death (Martin & Baehrecke, 2004; Liu et al ., 2007; LeBlanc & Saleh, 2009; Suganuma et al ., 2011). In the control B. mori larvae, relative expression of caspase showed marginal positive correlation with that of Atg5 gene ( R 2 =0.36), whereas it showed larger positive correlation ( R 2 =0.76) with AIF expression (table 2).…”

“…2c) confirming that apoptosis is mediated by a combined action of AIF and caspase. However, the relation and/or regulation between caspase expression and other genes become void after the infection (table 2) showing derailing of regulation on caspase activity under the parasitic influence (Castino et al ., 2005; LeBlanc & Saleh, 2009). Similar loss of co-regulation of other host-response genes with caspase expression was reported (Anitha et al ., 2013).…”