Microheterogeneity in the Kinetics and Sex-Specific Response to Type I IFN

Shani T. Gal-Oz, Alev Baysoy, Brinda Vijaykumar, Sara Mostafavi, Christophe Benoist, Tal Shay

Research output: Contribution to journalArticlepeer-review

Abstract

The response to type I IFNs involves the rapid induction of prototypical IFN signature genes (ISGs). It is not known whether the tightly controlled ISG expression observed at the cell population level correctly represents the coherent responses of individual cells or whether it masks some heterogeneity in gene modules and/or responding cells. We performed a time-resolved single-cell analysis of the first 3 h after in vivo IFN stimulation in macrophages and CD4+ T and B lymphocytes from mice. All ISGs were generally induced in concert, with no clear cluster of faster- or slower-responding ISGs. Response kinetics differed between cell types: mostly homogeneous for macrophages, but with far more kinetic diversity among B and T lymphocytes, which included a distinct subset of nonresponsive cells. Velocity analysis confirmed the differences between macrophages in which the response progressed throughout the full 3 h, versus B and T lymphocytes in which it was rapidly curtailed by negative feedback and revealed differences in transcription rates between the lineages. In all cell types, female cells responded faster than their male counterparts. The ISG response thus seems to proceed as a homogeneous gene block, but with kinetics that vary between immune cell types and with sex differences that might underlie differential outcomes of viral infections. The Journal of Immunology, 2024, 213: 96-104.

Original languageAmerican English
Pages (from-to)96-104
Number of pages9
JournalJournal of Immunology
Volume213
Issue number1
DOIs
StatePublished - 1 Jul 2024

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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