Innate Lymphoid Cells and Interferons Limit Neurologic and Articular Complications of Brucellosis

Am J Pathol. 2023 Sep;193(9):1170-1184. doi: 10.1016/j.ajpath.2023.05.006. Epub 2023 May 30.


Brucellosis is a globally significant zoonotic disease. Human patients with brucellosis develop recurrent fever and focal complications, including arthritis and neurobrucellosis. The current study investigated the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis caused by Brucella melitensis. After footpad infection, natural killer cells and ILC1 cells both limited joint colonization by Brucella. Mice lacking natural killer cells, and in particular mice lacking all ILCs, also developed marked arthritis after footpad infection. Following pulmonary infection, mice lacking adaptive immune cells and ILCs developed arthritis, neurologic complications, and meningitis. Adaptive immune cells and ILCs both limited colonization of the brain by Brucella following pulmonary infection. Transcriptional analysis of Brucella-infected brains revealed marked up-regulation of genes associated with inflammation and interferon responses, as well as down-regulation of genes associated with neurologic function. Type II interferon deficiency resulted in colonization of the brain by Brucella, but mice lacking both type I and type II interferon signaling more rapidly developed clinical signs of neurobrucellosis, exhibited hippocampal neuronal loss, and had higher levels of Brucella in their brains than mice lacking type II interferon signaling alone. Collectively, these findings indicate ILCs and interferons play an important role in prevention of focal complications during Brucella infection, and that mice with deficiencies in ILCs or interferons can be used to study pathogenesis of neurobrucellosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arthritis* / complications
  • Brucellosis* / complications
  • Brucellosis* / prevention & control
  • Humans
  • Immunity, Innate
  • Interferon-gamma
  • Interferons
  • Lymphocytes / pathology
  • Mice


  • Interferons
  • Interferon-gamma