Single-cell landscape of peripheral immune responses to fatal SFTS

Cell Rep. 2021 Nov 23;37(8):110039. doi: 10.1016/j.celrep.2021.110039.


Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high fatality. Poor prognosis of SFTS has been associated with dysregulated host immunity; however, the immune patterns associated with pathophysiology involving SFTS exacerbation remain unclear. Here, we show that the single-cell landscape of peripheral immune responses is reprogrammed in SFTS and characterized by monocyte shift to an intermediate type along with complement activation, perturbation of plasmablast composition, and highly exhausted T cells, all correlated with lethal consequences. We identify the overexpression of interferon (IFN)-stimulated genes across most immune cell types after SFTSV infection, which are simultaneously related to older age, high viremia, and a hyperinflammatory response. A retrospective clinical study reveals no efficiency of IFN-α in treating SFTS. These data collectively support the intermediate monocytes and IFN-I-inducible plasmablasts to be major targets for SFTS virus infection, and they indicate the pivotal role of the IFN-I response in exacerbating hyperinflammation and lethal SFTS.

Keywords: emerging infectious diseases; hemorrhagic fever; peripheral immune responses; scRNA-seq; severe fever with thrombocytopenia syndrome; tick-borne dieseases; type I interferon response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents
  • China / epidemiology
  • Cohort Studies
  • Complement Activation / immunology
  • Female
  • Humans
  • Immunity / immunology*
  • Immunity / physiology
  • Interferons / genetics
  • Leukocytes, Mononuclear / immunology*
  • Male
  • Monocytes / immunology
  • Plasma Cells
  • Retrospective Studies
  • Severe Fever with Thrombocytopenia Syndrome / epidemiology
  • Severe Fever with Thrombocytopenia Syndrome / immunology*
  • Single-Cell Analysis / methods
  • T-Lymphocytes / immunology
  • Viremia


  • Antiviral Agents
  • Interferons