Sex-associated Early-life viral Innate Immune Response is Transcriptionally Associated with chromatin remodeling of Type-I IFN-inducible Genes

Carrie-Anne Malinczak; Wendy Fonseca; Mohamed M. Mire; Abhijit Parolia; Arul Chinnaiyan; Andrew J. Rasky; Susan Morris; Kazuma Yagi; Jennifer R. Bermick; Nicholas W. Lukacs

doi:10.1016/j.mucimm.2023.06.002

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Sex-associated Early-life viral Innate Immune Response is Transcriptionally Associated with chromatin remodeling of Type-I IFN-inducible Genes

Journal article

Open access

Peer reviewed

Sex-associated Early-life viral Innate Immune Response is Transcriptionally Associated with chromatin remodeling of Type-I IFN-inducible Genes

Carrie-Anne Malinczak, Wendy Fonseca, Mohamed M. Mire, Abhijit Parolia, Arul Chinnaiyan, Andrew J. Rasky, Susan Morris, Kazuma Yagi, Jennifer R. Bermick and Nicholas W. Lukacs

Mucosal immunology, Vol.16(5), pp.578-592

10/2023

DOI: 10.1016/j.mucimm.2023.06.002

PMCID: PMC10646734

PMID: 37302711

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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.

Epigenetics

dendritic cells

innate immunity

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 Pathology
Wendy Fonseca - Department of Pathology
Mohamed M. Mire - Department of Pathology
Abhijit Parolia - Department of Pathology
Arul Chinnaiyan - Department of Pathology
Andrew J. Rasky - Department of Pathology
Susan Morris - Department of Pathology
Kazuma Yagi - Department of Pathology
Jennifer R. Bermick - University of Iowa
Nicholas W. Lukacs - Department of Pathology
Resource Type: Journal article
Publication Details: Mucosal immunology, Vol.16(5), pp.578-592
DOI: 10.1016/j.mucimm.2023.06.002
PMID: 37302711
PMCID: PMC10646734
NLM abbreviation: Mucosal Immunol
ISSN: 1933-0219
eISSN: 1935-3456
Publisher: Elsevier Inc
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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