Blockade Of PD-1 Attenuated Postsepsis Aspergillosis Via The Activation of IFN-γ and The Dampening of IL-10

Shock. 2020 Apr;53(4):514-524. doi: 10.1097/SHK.0000000000001392.


Background: Nosocomial aspergillosis in patients with sepsis has emerged in the past few years. Blockade of PD-1/PD-L pathway has tended to become a promising therapeutic strategy as it improved the outcome of bacterial sepsis and postsepsis secondary fungal infection. Recently, the controversial effects of PD-1 blockade on infectious diseases, including aspergillosis, have been demonstrated; therefore, the efficacy of anti-PD-1 drug still remains to be elucidated.

Methods: Cecal ligation and puncture (CLP) was conducted as a mouse sepsis model. Aspergillus fumigatus spores were intravenously inoculated on day 5 post-CLP, when the immune cells succumbed to exhaustion. Amphotericin B was medicated together with or without anti-PD-1 treatment after Aspergillus infection.

Results: Amphotericin B alone was not effective to treat the CLP-mice with secondary aspergillosis. In contrast, antifungal medication with the adjunctive anti-PD-1 treatment attenuated the fungal burdens in blood and internal organs, and improved the survival rate of the mice with secondary aspergillosis. These outcomes of PD-1 blockade were concurring with the enhanced CD86 expression on splenocytes, the augmented serum IFN-γ, and the dampened IL-10. Activated T cells from anti-PD-1-treated mice also highly increased IFN-γ and diminished IL-10 production.

Conclusion: The blockade of PD-1 on postsepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Aspergillosis / blood
  • Aspergillosis / etiology
  • Aspergillosis / prevention & control*
  • Aspergillus fumigatus
  • Disease Models, Animal
  • Female
  • Immunologic Factors / therapeutic use
  • Interferon-gamma / blood*
  • Interleukin-10 / blood*
  • Mice
  • Mice, Inbred C57BL
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Sepsis / blood
  • Sepsis / complications*
  • Sepsis / therapy


  • Antibodies, Monoclonal
  • Immunologic Factors
  • Programmed Cell Death 1 Receptor
  • Interleukin-10
  • Interferon-gamma