Exacerbation of hepatic injury during rodent malaria by myeloid-related protein 14

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Haruka Mizobuchi1, Wataru Fujii2, Shoko Isokawa1

  • 1Laboratory of Molecular Immunology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Plos One
|June 15, 2018
PubMed

Insights

Myeloid-related protein (MRP) 14 exacerbates liver injury in malaria by increasing inflammatory cells and molecules. This protein amplifies the inflammatory cascade, leading to significant hepatic dysfunction during rodent malaria.

Area of Science:

  • Immunology
  • Pathology
  • Infectious Diseases

Background:

  • Severe malaria often presents with hepatic dysfunction, but the underlying mechanisms remain unclear.
  • Myeloid-related protein (MRP) 14, a protein expressed by myeloid cells, is implicated in inflammatory diseases and elevated in malaria-infected mice.
  • Extracellular MRP14's role in malaria-induced liver injury requires investigation.

Purpose of the Study:

  • To determine if extracellular myeloid-related protein (MRP) 14 contributes to hepatic injury during rodent malaria.
  • To investigate the effects of administering recombinant MRP14 (rMRP14) on liver pathology in Plasmodium berghei ANKA-infected mice.

Main Methods:

  • Intravenous administration of rMRP14 to mice infected with Plasmodium berghei ANKA.
  • Assessment of parasite load, hematocrit, and serum hepatic enzymes.
  • Immunohistochemical analysis for macrophage accumulation.
  • Measurement of pro-inflammatory molecules (iNOS, IL-1β, IL-12, TNF-α) in the liver.

Main Results:

  • rMRP14 administration exacerbated liver injury and increased serum hepatic enzymes without affecting parasite numbers or hematocrit.
  • Increased accumulation of MRP14+ macrophages was observed in the livers of rMRP14-treated infected mice.
  • rMRP14 promoted the upregulation of pro-inflammatory molecules and nitric oxide (NO) in the liver, even in non-infected mice.

Conclusions:

  • Myeloid-related protein (MRP) 14 plays a key role in liver inflammation during rodent malaria.
  • MRP14 promotes the accumulation of MRP14+ cells and enhances pro-inflammatory responses, amplifying the inflammatory cascade and leading to hepatic injury.
  • MRP14 is a critical mediator of liver pathology in malaria.

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