Abstract
Type 1 interferon signaling influences monocyte/macrophage H3K4me3 and antiviral function throughout the lifespan 4619
The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832276
11/01/2025
DOI: 10.1093/jimmun/vkaf283.2276
Abstract
Abstract Description
The neonatal immune response is distinct from that of adults, with defects in both the innate and adaptive immune systems. Monocytes and macrophages are central to innate immune responses and demonstrate a developmental stage-specific gain in H3K4me3 at immunologically important gene promoters. This developmental gain is associated with more functional pathogen responses as development progresses from neonate to adult, but the factors underlying this are unclear. The intestinal microbiota drives tonic type 1 interferon signaling (IFN-I), which is critical for appropriate immune homeostasis and function. IFN-I signaling also guides innate immune cell H3K4me3 deposition, but this has not been studied in neonatal cells. Using mice that lack IFN-I signaling (IFNAR-/-) or have constitutive low-grade IFN-I expression (IRGM1-/-), we found that neonatal (P4-5), infant (P12-16) and adult (8 weeks) splenic monocyte/macrophage H3K4me3 patterning at key antiviral response genes depends on intact IFN-I signaling. The antiviral genes OAS1A, OAS2, OAS3 and IFI27l2 had increased promoter H3K4me3 in IRGM1-/- mice with decreased H3K4me3 in IFNAR-/- mice compared to WT controls at all developmental stages. These differences were associated with improved in vitro antiviral responses and improved in vivo survival in IRGM1-/- mice following Influenza A (PR8) infection. This highlights the importance of appropriate IFN-I signaling in immune cell development and function throughout the lifespan.
Funding Sources
NIH 5R01AI141673-05
Topic Categories
Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)
Details
- Title: Subtitle
- Type 1 interferon signaling influences monocyte/macrophage H3K4me3 and antiviral function throughout the lifespan 4619
- Creators
- Kara Misel-Wuchter - University of IowaJessica Knobbe - University of IowaKyra P. Watral - University of IowaJennifer Bermick - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832276
- DOI
- 10.1093/jimmun/vkaf283.2276
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Oxford University Press
- Grant note
- NIH: 5R01AI141673-05
NIH 5R01AI141673-05
- Alternative title
- IMMUNOLOGY2025™ Abstracts
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9985034932202771
Metrics
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