Abstract
Type I interferons (IFN-I) are a major antiviral defense and are critical for the activation of the adaptive immune system. However, early viral clearance by IFN-I could limit antigen availability, which could in turn impinge upon the priming of the adaptive immune system. In this study, we hypothesized that transient IFN-I blockade could increase antigen presentation after acute viral infection. To test this hypothesis, we infected mice with viruses coadministered with a single dose of IFN-I receptor–blocking antibody to induce a short-term blockade of the IFN-I pathway. This resulted in a transient “spike” in antigen levels, followed by rapid antigen clearance. Interestingly, short-term IFN-I blockade after coronavirus, flavivirus, rhabdovirus, or arenavirus infection induced a long-lasting enhancement of immunological memory that conferred improved protection upon subsequent reinfections. Short-term IFN-I blockade also improved the efficacy of viral vaccines. These findings demonstrate a novel mechanism by which IFN-I regulate immunological memory and provide insights for rational vaccine design.
| Original language | English (US) |
|---|---|
| Article number | 20191220 |
| Journal | Journal of Experimental Medicine |
| Volume | 217 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 7 2020 |
Funding
We thank Drs. Susan Weiss, Rafi Ahmed, Daniel Pinschewer, Chyung-Ru Wang, Richard D?Aquila, and Hank Seifert for discussions. This work was possible with grants from the Chicago Developmental Center for AIDS Research (P30 AI117943) and National Institutes of Health (1R21AI132848-01A1 and DP2DA051912) to P. Penaloza-MacMaster and a National Science Foundation Graduate Research Fellowship Program grant (DGE-1842165) to N. Palacio. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. Author contributions: P. Penaloza-MacMaster and N. Palacio designed and conducted the experiments and wrote the paper. T. Dangi, Y.R. Chung, Y. Wang, J.L. Loredo-Varela, and Z. Zhang conducted the experiments. Disclosures: N. Palacio and P. Penaloza-MacMaster reported that a provisional patent application was submitted (transient interferon blockade to enhance immune responses to antigens and improve vaccines). No other disclosures were reported. This work was possible with grants from the Chicago Developmental Center for AIDS Research (P30 AI117943) and National Institutes of Health (1R21AI132848-01A1 and DP2DA051912) to P. Penaloza-MacMaster and a National Science Foundation Graduate Research Fellowship Program grant (DGE-1842165) to N. Palacio. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
