Type I interferon production enhances susceptibility to Listeria monocytogenes infection.
Numerous bacterial products such as lipopolysaccharide potently induce type I interferons (IFNs); however, the contribution of this innate response to host defense against bacterial infection remains unclear. Although mice deficient in either IFN regulatory factor (IRF)3 or the type I IFN receptor (IFNAR)1 are highly susceptible to viral infection, we show that these mice exhibit a profound resistance to infection caused by the Gram-positive intracellular bacterium Listeria monocytogenes compared with wild-type controls. Furthermore, this enhanced bacterial clearance is accompanied by a block in L. monocytogenes-induced splenic apoptosis in IRF3- and IFNAR1-deficient mice. Thus, our results highlight the disparate roles of type I IFNs during bacterial versus viral infections and stress the importance of proper IFN modulation in host defense.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 8-240 Factor Bldg., 10833 Le Conte Ave., 90095, USA.
Ryan M
RM
O'Connell
Supriya K
SK
Saha
Sagar A
SA
Vaidya
Kevin W
KW
Bruhn
Gustavo A
GA
Miranda
Brian
B
Zarnegar
Andrea K
AK
Perry
Bidong O
BO
Nguyen
Timothy F
TF
Lane
Tadatsugu
T
Taniguchi
Jeff F
JF
Miller
Genhong
G
Cheng
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction / Q000379:methods; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency*; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C508032:Ifnar1 protein, mouse; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C494233:Irf3 protein, mouse; D008565:Membrane Proteins; D017471:Receptors, Interferon; D014157:Transcription Factors; D053633:Receptor, Interferon alpha-beta