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Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes.
Malinczak, Carrie-Anne; Fonseca, Wendy; Mire, Mohamed M; Parolia, Abhijit; Chinnaiyan, Arul; Rasky, Andrew J; Morris, Susan; Yagi, Kazuma; Bermick, Jennifer R; Lukacs, Nicholas W.
Afiliación
  • Malinczak CA; Department of Pathology, University of Michigan, Ann Arbor, USA.
  • Fonseca W; Department of Pathology, University of Michigan, Ann Arbor, USA.
  • Mire MM; Department of Pathology, University of Michigan, Ann Arbor, USA.
  • Parolia A; Department of Pathology, University of Michigan, Ann Arbor, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA.
  • Chinnaiyan A; Department of Pathology, University of Michigan, Ann Arbor, USA; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, USA.
  • Rasky AJ; Department of Pathology, University of Michigan, Ann Arbor, USA.
  • Morris S; Department of Pathology, University of Michigan, Ann Arbor, USA.
  • Yagi K; Department of Pathology, University of Michigan, Ann Arbor, USA.
  • Bermick JR; Department of Pediatrics, University of Iowa, Iowa City, USA.
  • Lukacs NW; Department of Pathology, University of Michigan, Ann Arbor, USA; Mary H Weiser Food Allergy Center, University of Michigan, Ann Arbor, USA. Electronic address: nlukacs@umich.edu.
Mucosal Immunol ; 16(5): 578-592, 2023 10.
Article en En | MEDLINE | ID: mdl-37302711
This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon respiratory syncytial virus (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/ interleukin (Il12a) and enhanced IFNAR1+ expression in BMDC from early-life RSV-infected female mice that leads to increased IFN-γ production by T cells. Phenotypic differences were verified upon pulmonary sensitization whereby EL-RSV male-derived BMDC promoted enhanced T helper 2/17 responses and exacerbated disease upon RSV infection while EL-RSV/F BMDC sensitization was relatively protective. Assay for transposase-accessible chromatin using sequencing analysis (ATAC-seq) demonstrated that EL-RSV/F BMDC had enhanced chromatin accessibility near type-I immune genes with JUN, STAT1/2, and IRF1/8 transcription factors predicted to have binding sites in accessible regions. Importantly, ATAC-seq of human cord blood-derived monocytes displayed a similar sex-associated chromatin landscape with female-derived monocytes having more accessibility in type-I immune genes. These studies enhance our understanding of sex-associated differences in innate immunity by epigenetically controlled transcriptional programs amplified by early-life infection in females via type-I immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Infecciones por Virus Sincitial Respiratorio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Infecciones por Virus Sincitial Respiratorio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos