Type I IFN (IFN-α/β) is thought to enhance growth of the foodborne intracellular pathogen Listeria monocytogenes by promoting mechanisms that dampen innate immunity to infection. However, the type I IFN response has been studied primarily using methods that bypass the stomach and, therefore, fail to replicate the natural course of L. monocytogenes infection. In this study, we compared i.v. and foodborne transmission of L. monocytogenes in mice lacking the common type I IFN receptor (IFNAR1-/-). Contrary to what was observed using i.v. infection, IFNAR1-/- and wild-type mice had similar bacterial burdens in the liver and spleen following foodborne infection. Splenocytes from wild-type mice infected i.v. produced significantly more IFN-β than did those infected by the foodborne route. Consequently, the immunosuppressive effects of type I IFN signaling, which included T cell death, increased IL-10 secretion, and repression of neutrophil recruitment to the spleen, were all observed following i.v. but not foodborne transmission of L. monocytogenes. Type I IFN was also previously shown to cause a loss of responsiveness to IFN-γ through downregulation of the IFN-γ receptor a-chain on macrophages and dendritic cells. However, we detected a decrease in surface expression of IFN-γ receptor a-chain even in the absence of IFN-α/β signaling, suggesting that in vivo, this infectioninduced phenotype is not type I IFN-dependent. These results highlight the importance of using the natural route of infection for studies of host-pathogen interactions and suggest that the detrimental effects of IFN-α/β signaling on the innate immune response to L. monocytogenes may be an artifact of the i.v. infection model.
|Number of pages||8|
|Journal||Journal of Immunology|
|State||Published - Apr 1 2016|
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health Grant AI101373 (to S.E.F.D.). We are grateful to Grant Jones and Dr. David Horohov for critical review of this manuscript. We also thank Greg Bauman and Emily Rubinson for technical assistance.
Copyright © 2016 by The American Association of Immunologists, Inc.
ASJC Scopus subject areas
- Immunology and Allergy