RGD Reference Report - An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity. - Rat Genome Database

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An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.

Authors: Li, Xiao-Ling  Ezelle, Heather J  Kang, Tae-Jin  Zhang, Lei  Shirey, Kari Ann  Harro, Janette  Hasday, Jeffrey D  Mohapatra, Saroj K  Crasta, Oswald R  Vogel, Stefanie N  Cross, Alan S  Hassel, Bret A 
Citation: Li XL, etal., Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20816-21. doi: 10.1073/pnas.0807265105. Epub 2008 Dec 15.
RGD ID: 40902812
Pubmed: PMID:19075243   (View Abstract at PubMed)
PMCID: PMC2634919   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0807265105   (Journal Full-text)

Type I IFNs were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of IFN antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of IFN-induced antiviral activity. Here, we identify a role for RNase-L in the host antibacterial response. RNase-L(-/-) mice exhibited a dramatic increase in mortality after challenge with Bacillus anthracis and Escherichia coli; this increased susceptibility was due to a compromised immune response resulting in increased bacterial load. Investigation of the mechanisms of RNase-L antibacterial activity indicated that RNase-L is required for the optimal induction of proinflammatory cytokines that play essential roles in host defense from bacterial pathogens. RNase-L also regulated the expression of the endolysosomal protease, cathepsin-E, and endosome-associated activities, that function to eliminate internalized bacteria and may contribute to RNase-L antimicrobial action. Our results reveal a unique role for RNase-L in the antibacterial response that is mediated through multiple mechanisms. As a regulator of fundamental components of the innate immune response, RNase-L represents a viable therapeutic target to augment host defense against diverse microbial pathogens.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1BHumananthrax disease disease_progressionISOIl1b (Mus musculus)mRNA:decreased expression:multiple (mouse)RGD 
Il1bMouseanthrax disease disease_progressionIEP mRNA:decreased expression:multiple (mouse)RGD 
Il1bRatanthrax disease disease_progressionISOIl1b (Mus musculus)mRNA:decreased expression:multiple (mouse)RGD 
RNASELHumananthrax disease severityISORnasel (Mus musculus) RGD 
RnaselRatanthrax disease severityISORnasel (Mus musculus) RGD 
RnaselMouseanthrax disease severityIMP  RGD 
TNFHumananthrax disease disease_progressionISOTnf (Mus musculus)protein:decreased expression:multiple (mouse)RGD 
TnfRatanthrax disease disease_progressionISOTnf (Mus musculus)protein:decreased expression:multiple (mouse)RGD 
TnfMouseanthrax disease disease_progressionIEP protein:decreased expression:multiple (mouse)RGD 
RNASELHumanEscherichia Coli Infections severityISORnasel (Mus musculus) RGD 
RnaselMouseEscherichia Coli Infections severityIMP  RGD 
RnaselRatEscherichia Coli Infections severityISORnasel (Mus musculus) RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IFNB1Humanlipopolysaccharide increases expression ISOIfnb1 (Mus musculus)lipopolysaccharide increases expression of IFNb1 mRNA in macrophagesRGD 
IL1BHumanlipopolysaccharide increases expression ISOIl1b (Mus musculus)lipopolysaccharide increases expression of Il1b mRNA in macrophagesRGD 
Ifnb1Ratlipopolysaccharide increases expression ISOIfnb1 (Mus musculus)lipopolysaccharide increases expression of IFNb1 mRNA in macrophagesRGD 
Ifnb1Mouselipopolysaccharide increases expression EXP lipopolysaccharide increases expression of IFNb1 mRNA in macrophagesRGD 
Il1bRatlipopolysaccharide increases expression ISOIl1b (Mus musculus)lipopolysaccharide increases expression of Il1b mRNA in macrophagesRGD 
Il1bMouselipopolysaccharide increases expression EXP lipopolysaccharide increases expression of Il1b mRNA in macrophagesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifnb1  (interferon beta 1)
Il1b  (interleukin 1 beta)
Rnasel  (ribonuclease L)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Ifnb1  (interferon beta 1, fibroblast)
Il1b  (interleukin 1 beta)
Rnasel  (ribonuclease L (2', 5'-oligoisoadenylate synthetase-dependent))
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
IFNB1  (interferon beta 1)
IL1B  (interleukin 1 beta)
RNASEL  (ribonuclease L)
TNF  (tumor necrosis factor)


Additional Information