A Role for the Human Nucleotide-binding Domain, Leucine-rich Repeat-containing Family Member NLRC5 in Antiviral Responses

Neerincx, Andreas; Lautz, Katja; Menning, Maureen; Kremmer, Elisabeth; Zigrino, Paola; Hösel, Marianna; Büning, Hildegard; Schwarzenbacher, Robert; Kufer, Thomas A.

doi:10.1074/jbc.m110.109736

Cited by 149 publications

(228 citation statements)

References 38 publications

(48 reference statements)

Supporting

Mentioning

212

Contrasting

Order By: Relevance

“…The role of NLRC5 in innate immunity is still not well understood, but it is known to participate in both the innate and adaptive immune responses [96][97][98][99][100]. In HeLa and THP-1 cells, NLRC5 has been demonstrated to positively regulate the IFN pathway, whereas in other models such as HEK 293 cells and RAW 264.7 cells, NLRC5 has been demonstrated to negatively regulate the IFN, NF-jB, and AP-1 pathways [96][97][98]100]. In RAW 264.7 cells, it was demonstrated that the interaction of NLRC5 with IKKa results in the inhibition of its catalytic activity.…”

Section: Nlrc5mentioning

confidence: 99%

Inflammasomes and its importance in viral infections

León-Juárez²,

et al. 2016

View full text Add to dashboard Cite

A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1. The inflammasome operates as a platform for caspase-1 activation, resulting in caspase-1-dependent proteolytic maturation and secretion of interleukin (IL)-1b and IL-18. This, in turn, activates the expression of other immune genes and facilitates lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Moreover, inflammasomes counter viral replication and remove infected immune cells through an inflammatory cell death, program termed as pyroptosis. As a countermeasure, viral pathogens have evolved virulence factors to antagonise inflammasome pathways. In this review, we discuss the role of inflammasomes in sensing viral infection as well as the evasion strategies that viruses have developed to evade inflammasome-dependent immune responses. This information summarises our understanding of host defence mechanisms against viruses and highlights research areas that can provide new approaches to interfere in the pathogenesis of viral diseases.

show abstract

Section: Nlrc5mentioning

confidence: 99%

Inflammasomes and its importance in viral infections

León-Juárez²,

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Over the past two years, several in vitro studies reported the roles of NLRC5 in immune regulation and host defense [8,9]. NLRC5 can be upregulated by IFN-γ and bacterial or viral pathogens [3,10,11]. NLRC5 was originally found to negatively regulate the NF-κB and type I interferonproducing signaling pathways by targeting the IKK complex and RIG-I/MDA5, respectively [12].…”

Section: Introductionmentioning

confidence: 99%

NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens

et al. 2012

View full text Add to dashboard Cite

NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection. NLRC5, the largest member of the NLR family, has recently attracted much attention. However, in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways. The in vivo function of NLRC5 remains unknown. Here, we report that NLRC5 is a critical regulator of host defense against intracellular pathogens in vivo. NLRC5 was specifically required for the expression of genes involved in MHC class I antigen presentation. NLRC5-deficient mice showed a profound defect in the expression of MHC class I genes and a concomitant failure to activate L. monocytogenes-specific CD8 + T cell responses, including activation, proliferation and cytotoxicity, and the mutant mice were more susceptible to the pathogen infection. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for pathogen-induced expression of NF-κB-dependent pro-inflammatory genes as well as type I interferon genes. Thus, NLRC5 critically regulates MHC class I antigen presentation to control intracellular pathogen infection.

show abstract

“…NLRC5 is also expressed abundantly in lung and intestine, which have close contact with microorganism. More specifically, NLRC5 is found highly expressed in immune cells including mouse primary cells such as bone marrow-derived macrophages (BMDMs), splenic DCs, CD4 + T cells, CD8 + T cells and B cells as well as in cell lines such as human THP-1, Jurkat T cells, Raji B cells and mouse RAW264.7 (Benko et al, 2010;Cui et al, 2010;Neerincx et al, 2010). While NLRC5 is constitutively expressed in many immune cells, it can also be dramatically induced by a variety of stimulations.…”

Section: Expression Of Nlrc5mentioning

confidence: 99%

“…While NLRC5 is constitutively expressed in many immune cells, it can also be dramatically induced by a variety of stimulations. Interferon-γ (IFN-γ) is a widely reported stimulus capable of strongly inducing NLRC5 expression at both mRNA and protein level in various cell types like lymphocytes (CD4 + T cells, CD8 + T cells), myeloid cells (macrophage or dendritic cells), fibroblasts and Hela cells (Benko et al, 2010;Neerincx et al, 2010;Staehli et al, 2012). LPS is also confi rmed to induce a high level of NLRC5 transcription and expression (Cui et al, 2010;Staehli et al, 2012;Yao et al, 2012).…”

Section: Expression Of Nlrc5mentioning

confidence: 99%

“…While the role of NLRC5 in regulating MHC class I gene expression is well recognized by intensive studies, previous researches suggested that NLRC5 may also regulate innate immune responses through affecting TLR mediated NF-κB activation, type I interferon (IFN)-producing pathways as well as inflammasome activation (Benko et al, 2010;Cui et al, 2010;Neerincx et al, 2010;Davis et al, 2011;Lamkanfi and Kanneganti, 2012).Two studies showed NLRC5 was a positive regulator of type I IFN producing pathway in human fi broblasts and THP-1 cells (Kuenzel et al, 2010;Neerincx et al, 2010). However, NLRC5 was shown to suppress type I IFN production through association with RIG-I and MDA5 (the dsRNA sensors), or inhibit NF-κB pathway through its direct binding with IκB kinase-α (IKK-α) and IKK-β (Cui et al, 2010).…”

Section: Function Of Nlrc5 In Innate Immune Responsementioning

confidence: 99%

See 1 more Smart Citation

Expression regulation and function of NLRC5

Yao

Qian

2013

Protein Cell

View full text Add to dashboard Cite

The NOD like receptors (NLRs), a class of intracellular receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5, the largest member of the NLR protein family, has recently been identified as a critical regulator of immune responses. While NLRC5 is constitutively and widely expressed, it can be dramatically induced by interferons during pathogen infections. Both in vitro and in vivo studies have demonstrated that NLRC5 is a specifi c and master regulator of major mistocompatibility complex (MHC) class I genes as well as related genes involved in MHC class I antigen presentation. The expression of MHC class I genes is regulated by NLRC5 in coordination with the RFX components through an enhanceosome-dependent manner. And the involvement of NLRC5 in MHC class I mediated CD8 + T cell activation, proliferation and cytotoxicity is proved to be critical for host defense against intracellular bacterial infections. Nevertheless, the role of NLRC5 in innate immunity remains to be further explored. Here, we review the research advances on the structure, expression regulation and function of NLRC5.

show abstract

A Role for the Human Nucleotide-binding Domain, Leucine-rich Repeat-containing Family Member NLRC5 in Antiviral Responses

Cited by 149 publications

References 38 publications

Inflammasomes and its importance in viral infections

Inflammasomes and its importance in viral infections

NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens

Expression regulation and function of NLRC5

Contact Info

Product

Resources

About