Journal article
Sex-associated Early-life viral Innate Immune Response is Transcriptionally Associated with chromatin remodeling of Type-I IFN-inducible Genes
Mucosal immunology, Vol.16(5), pp.578-592
10/2023
DOI: 10.1016/j.mucimm.2023.06.002
PMCID: PMC10646734
PMID: 37302711
Abstract
Differential immune responses between the sexes are observed throughout life. This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDC). BMDC grown from 7-day old mice show enhanced type-1 IFN signaling in female compared to male BMDC. Upon RSV infection of 7-day old mice, a significantly altered phenotype of BMDC at 4 weeks post-infection is observed in a sex-dependent manner. The alterations include heightened Ifnb/Il12a and enhanced IFNAR1+ expression in BMDC from early-life RSV infected female mice (EL-RSV/F) that leads to increased IFN-γ production by T cells. Phenotypic differences were verified upon pulmonary sensitization whereby EL-RSV male-derived (EL-RSV/M) BMDC promoted enhanced Th2/17 responses and exacerbated disease upon RSV infection while EL-RSV/F BMDC sensitization was relatively protective. ATAC-seq analysis demonstrated that EL-RSV/F BMDC had enhanced chromatin accessibility near type-1 immune genes with JUN, STAT1/2 and IRF1/8 transcription factors predicted to have binding sites in accessible regions. Importantly, ATAC-seq analysis of human cord blood-derived monocytes displayed a similar sex-associated chromatin landscape with female-derived monocytes having more accessibility in type-1 immune genes. These studies enhance our understanding of sex-associated differences of innate immunity that promotes an epigenetically controlled transcriptional program amplified by early-life infection in females via type-1 immunity.
Details
- Title: Subtitle
- Sex-associated Early-life viral Innate Immune Response is Transcriptionally Associated with chromatin remodeling of Type-I IFN-inducible Genes
- Creators
- Carrie-Anne Malinczak - Department of PathologyWendy Fonseca - Department of PathologyMohamed M. Mire - Department of PathologyAbhijit Parolia - Department of PathologyArul Chinnaiyan - Department of PathologyAndrew J. Rasky - Department of PathologySusan Morris - Department of PathologyKazuma Yagi - Department of PathologyJennifer R. Bermick - University of IowaNicholas W. Lukacs - Department of Pathology
- Resource Type
- Journal article
- Publication Details
- Mucosal immunology, Vol.16(5), pp.578-592
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.mucimm.2023.06.002
- PMID
- 37302711
- PMCID
- PMC10646734
- ISSN
- 1933-0219
- eISSN
- 1935-3456
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: HL158001-01, RO1AI138348, R35HL150682, PO1AI089473
- Language
- English
- Electronic publication date
- 06/09/2023
- Date published
- 10/2023
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984430332402771
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