STAT4 is expressed in neutrophils and promotes antimicrobial immunity

JCI Insight. 2021 Jul 22;6(14):e141326. doi: 10.1172/jci.insight.141326.


Signal transducer and activator of transcription 4 (STAT4) is expressed in hematopoietic cells and plays a key role in the differentiation of T helper 1 cells. Although STAT4 is required for immunity to intracellular pathogens, the T cell-independent protective mechanisms of STAT4 are not clearly defined. In this report, we demonstrate that STAT4-deficient mice were acutely sensitive to methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that STAT4 was expressed in neutrophils and activated by IL-12 via a JAK2-dependent pathway. We demonstrate that STAT4 was required for multiple neutrophil functions, including IL-12-induced ROS production, chemotaxis, and production of the neutrophil extracellular traps. Importantly, myeloid-specific and neutrophil-specific deletion of STAT4 resulted in enhanced susceptibility to MRSA, demonstrating the key role of STAT4 in the in vivo function of these cells. Thus, these studies identify STAT4 as an essential regulator of neutrophil functions and a component of innate immune responses in vivo.

Keywords: Immunology; Neutrophils.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Immunity, Innate
  • Interleukin-12 / metabolism
  • Janus Kinase 2 / metabolism
  • MAP Kinase Signaling System / immunology
  • Methicillin-Resistant Staphylococcus aureus / immunology*
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / metabolism*
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology


  • STAT4 Transcription Factor
  • Stat4 protein, mouse
  • Interleukin-12
  • Jak2 protein, mouse
  • Janus Kinase 2