IL-1α promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria

Sci Rep. 2019 May 20;9(1):7575. doi: 10.1038/s41598-019-44125-2.

Abstract

Malaria causes hepatic inflammation and damage, which contribute to disease severity. The pro-inflammatory cytokine interleukin (IL)-1α is released by non-hematopoietic or hematopoietic cells during liver injury. This study established the role of IL-1α in the liver pathology caused by blood-stage P. chabaudi malaria. During acute infection, hepatic inflammation and necrosis were accompanied by NLRP3 inflammasome-independent IL-1α production. Systemically, IL-1α deficiency attenuated weight loss and hypothermia but had minor effects on parasitemia control. In the liver, the absence of IL-1α reduced the number of TUNEL+ cells and necrotic lesions. This finding was associated with a lower inflammatory response, including TNF-α production. The main source of IL-1α in the liver of infected mice was inflammatory cells, particularly neutrophils. The implication of IL-1α in liver inflammation and necrosis caused by P. chabaudi infection, as well as in weight loss and hypothermia, opens up new perspectives for improving malaria outcomes by inhibiting IL-1 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Inflammation / immunology*
  • Inflammation / parasitology
  • Inflammation / pathology
  • Interleukin-1alpha / immunology*
  • Liver / immunology
  • Liver / parasitology
  • Liver / pathology*
  • Malaria / immunology*
  • Malaria / parasitology
  • Malaria / pathology
  • Male
  • Mice, Inbred C57BL
  • Necrosis
  • Plasmodium chabaudi / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Interleukin-1alpha
  • Tumor Necrosis Factor-alpha