Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes.
Listeria monocytogenes is a facultative intracellular pathogen that induces a cytosolic signaling cascade resulting in expression of interferon (IFN)-beta. Although type I IFNs are critical in viral defense, their role in immunity to bacterial pathogens is much less clear. In this study, we addressed the role of type I IFNs by examining the infection of L. monocytogenes in BALB/c mice lacking the type I IFN receptor (IFN-alpha/betaR-/-). During the first 24 h of infection in vivo, IFN-alpha/betaR-/- and wild-type mice were similar in terms of L. monocytogenes survival. In addition, the intracellular fate of L. monocytogenes in macrophages cultured from IFN-alpha/betaR-/- and wild-type mice was indistinguishable. However, by 72 h after inoculation in vivo, IFN-alpha/betaR-/- mice were approximately 1,000-fold more resistant to a high dose L. monocytogenes infection. Resistance was correlated with elevated levels of interleukin 12p70 in the blood and increased numbers of CD11b+ macrophages producing tumor necrosis factor alpha in the spleen of IFN-alpha/betaR-/- mice. The results of this study suggest that L. monocytogenes might be exploiting an innate antiviral response to promote its pathogenesis.
Department of Molecular and Cell Biology, 508 Barker Hall, University of California, Berkeley, 94720, USA.
Victoria
V
Auerbuch
Dirk G
DG
Brockstedt
Nicole
N
Meyer-Morse
Mary
M
O'Riordan
Daniel A
DA
Portnoy
D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008088:Listeriosis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction / Q000379:methods; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency*; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D017931:DNA Primers; D007370:Interferon Type I; D008565:Membrane Proteins; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D053633:Receptor, Interferon alpha-beta; D018664:Interleukin-12; D007371:Interferon-gamma