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.
Auerbuch
Victoria
V
Department of Molecular and Cell Biology, 508 Barker Hall, University of California, Berkeley, 94720, USA.
Brockstedt
Dirk G
DG
Meyer-Morse
Nicole
N
O'Riordan
Mary
M
Portnoy
Daniel A
DA
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