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Role of type I interferons in inflammasome activation, cell death, and disease during microbial infection.

Malireddi RK, Kanneganti TD - Front Cell Infect Microbiol (2013)

Bottom Line: Interferons (IFNs) were discovered over a half-century ago as antiviral factors.Deregulated type I IFN production results in a damaging cascade of cell death, inflammation, and immunological host responses that can lead to tissue injury and disease progression.Understanding the specific mechanisms driving type I IFN-mediated cell death and disease could aid in the development of targeted therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, St. Jude Children's Research Hospital Memphis, TN, USA.

ABSTRACT
Interferons (IFNs) were discovered over a half-century ago as antiviral factors. The role of type I IFNs has been studied in the pathogenesis of both acute and chronic microbial infections. Deregulated type I IFN production results in a damaging cascade of cell death, inflammation, and immunological host responses that can lead to tissue injury and disease progression. Here, we summarize the role of type I IFNs in the regulation of cell death and disease during different microbial infections, ranging from viruses and bacteria to fungal pathogens. Understanding the specific mechanisms driving type I IFN-mediated cell death and disease could aid in the development of targeted therapies.

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Related in: MedlinePlus

Role of type I interferons in inflammasome activation. Type I IFNs contribute to inflammasome activation through two different mechanisms. First, type I interferons are required for the upregulation of caspase-11, which contributes to activation of a non-canonical NLRP3 inflammasome in response to enteropathogenic bacteria, such as Citrobacter rodentium and Escherichia coli. Second, they prime the expression of inflammasome-forming NLRP3, RIG-I and AIM2 molecules for potentiating inflammasome activation.
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Figure 2: Role of type I interferons in inflammasome activation. Type I IFNs contribute to inflammasome activation through two different mechanisms. First, type I interferons are required for the upregulation of caspase-11, which contributes to activation of a non-canonical NLRP3 inflammasome in response to enteropathogenic bacteria, such as Citrobacter rodentium and Escherichia coli. Second, they prime the expression of inflammasome-forming NLRP3, RIG-I and AIM2 molecules for potentiating inflammasome activation.

Mentions: Type I IFNs are innate immune effector molecules with strong pro-inflammatory activities, and have been shown to contribute to the high mortality rates in septic shock syndromes (Karaghiosoff et al., 2003; Huys et al., 2009). Type I IFNs also contribute to inflammasome-dependent caspase-1 activation leading to pro-inflammatory pyroptotic cell death (Figure 2) (Anand et al., 2011; Franchi et al., 2012). There have been multiple different inflammasomes identified that sense a diverse array of microbial- and damage-associated PAMPs. These include the Naip-Nlrc4 inflammasome (Mariathasan et al., 2004; Kofoed and Vance, 2011; Zhao et al., 2011), the Nlrp1b inflammasome (Boyden and Dietrich, 2006; Masters et al., 2012), the Nlrp3 inflammasome (Kanneganti et al., 2006b; Mariathasan et al., 2006; Sutterwala et al., 2006; Anand et al., 2011), the Nlrp6 inflammasome (Elinav et al., 2011), the Nlrp12 inflammasome (Vladimer et al., 2012), the Aim2 inflammasome (Fernandes-Alnemri et al., 2010; Jones et al., 2010; Rathinam et al., 2010; Sauer et al., 2010), the RIG-I inflammasome (Poeck et al., 2010; Pothlichet et al., 2013), and the IFI16 inflammasome (Kerur et al., 2011). Inflammasome-dependent casapase-1 activation and pyroptosis are associated with the production of mature IL-1β and IL-18 cytokines, which generates a pro-inflammatory environment in host tissues (Figure 2). Inflammasome-dependent pyroptosis shares features of both apoptosis and necrosis and is tightly regulated by distinct signaling pathways.


Role of type I interferons in inflammasome activation, cell death, and disease during microbial infection.

Malireddi RK, Kanneganti TD - Front Cell Infect Microbiol (2013)

Role of type I interferons in inflammasome activation. Type I IFNs contribute to inflammasome activation through two different mechanisms. First, type I interferons are required for the upregulation of caspase-11, which contributes to activation of a non-canonical NLRP3 inflammasome in response to enteropathogenic bacteria, such as Citrobacter rodentium and Escherichia coli. Second, they prime the expression of inflammasome-forming NLRP3, RIG-I and AIM2 molecules for potentiating inflammasome activation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824101&req=5

Figure 2: Role of type I interferons in inflammasome activation. Type I IFNs contribute to inflammasome activation through two different mechanisms. First, type I interferons are required for the upregulation of caspase-11, which contributes to activation of a non-canonical NLRP3 inflammasome in response to enteropathogenic bacteria, such as Citrobacter rodentium and Escherichia coli. Second, they prime the expression of inflammasome-forming NLRP3, RIG-I and AIM2 molecules for potentiating inflammasome activation.
Mentions: Type I IFNs are innate immune effector molecules with strong pro-inflammatory activities, and have been shown to contribute to the high mortality rates in septic shock syndromes (Karaghiosoff et al., 2003; Huys et al., 2009). Type I IFNs also contribute to inflammasome-dependent caspase-1 activation leading to pro-inflammatory pyroptotic cell death (Figure 2) (Anand et al., 2011; Franchi et al., 2012). There have been multiple different inflammasomes identified that sense a diverse array of microbial- and damage-associated PAMPs. These include the Naip-Nlrc4 inflammasome (Mariathasan et al., 2004; Kofoed and Vance, 2011; Zhao et al., 2011), the Nlrp1b inflammasome (Boyden and Dietrich, 2006; Masters et al., 2012), the Nlrp3 inflammasome (Kanneganti et al., 2006b; Mariathasan et al., 2006; Sutterwala et al., 2006; Anand et al., 2011), the Nlrp6 inflammasome (Elinav et al., 2011), the Nlrp12 inflammasome (Vladimer et al., 2012), the Aim2 inflammasome (Fernandes-Alnemri et al., 2010; Jones et al., 2010; Rathinam et al., 2010; Sauer et al., 2010), the RIG-I inflammasome (Poeck et al., 2010; Pothlichet et al., 2013), and the IFI16 inflammasome (Kerur et al., 2011). Inflammasome-dependent casapase-1 activation and pyroptosis are associated with the production of mature IL-1β and IL-18 cytokines, which generates a pro-inflammatory environment in host tissues (Figure 2). Inflammasome-dependent pyroptosis shares features of both apoptosis and necrosis and is tightly regulated by distinct signaling pathways.

Bottom Line: Interferons (IFNs) were discovered over a half-century ago as antiviral factors.Deregulated type I IFN production results in a damaging cascade of cell death, inflammation, and immunological host responses that can lead to tissue injury and disease progression.Understanding the specific mechanisms driving type I IFN-mediated cell death and disease could aid in the development of targeted therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, St. Jude Children's Research Hospital Memphis, TN, USA.

ABSTRACT
Interferons (IFNs) were discovered over a half-century ago as antiviral factors. The role of type I IFNs has been studied in the pathogenesis of both acute and chronic microbial infections. Deregulated type I IFN production results in a damaging cascade of cell death, inflammation, and immunological host responses that can lead to tissue injury and disease progression. Here, we summarize the role of type I IFNs in the regulation of cell death and disease during different microbial infections, ranging from viruses and bacteria to fungal pathogens. Understanding the specific mechanisms driving type I IFN-mediated cell death and disease could aid in the development of targeted therapies.

Show MeSH
Related in: MedlinePlus