Type II alveolar cell MHCII improves respiratory viral disease outcomes while exhibiting limited antigen presentation

Nat Commun. 2021 Jun 28;12(1):3993. doi: 10.1038/s41467-021-23619-6.

Abstract

Type II alveolar cells (AT2s) are critical for basic respiratory homeostasis and tissue repair after lung injury. Prior studies indicate that AT2s also express major histocompatibility complex class II (MHCII) molecules, but how MHCII expression by AT2s is regulated and how it contributes to host defense remain unclear. Here we show that AT2s express high levels of MHCII independent of conventional inflammatory stimuli, and that selective loss of MHCII from AT2s in mice results in modest worsening of respiratory virus disease following influenza and Sendai virus infections. We also find that AT2s exhibit MHCII presentation capacity that is substantially limited compared to professional antigen presenting cells. The combination of constitutive MHCII expression and restrained antigen presentation may position AT2s to contribute to lung adaptive immune responses in a measured fashion, without over-amplifying damaging inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / immunology*
  • Animals
  • Antigen Presentation / immunology*
  • Antigen-Presenting Cells / immunology*
  • Cell Line
  • Dogs
  • Histocompatibility Antigens Class II / immunology
  • Inflammation / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Lung / cytology
  • Lung / immunology
  • Macaca mulatta
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Respirovirus Infections / immunology*
  • Respirovirus Infections / pathology
  • Sendai virus / immunology

Substances

  • Histocompatibility Antigens Class II