Related Experiment Video

Updated: Nov 16, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

11.1K

RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection

Hua-Rong Huang1,2, Soo Jung Cho1, Rebecca M Harris1

  • 1Department of Medicine, Pulmonary and Critical Care, Weill Cornell Medicine, New York, New York.

American Journal of Respiratory Cell and Molecular Biology
|February 24, 2021
PubMed

Insights

Receptor-interacting protein kinase 3 (RIPK3) is crucial for fighting Streptococcus pneumoniae pneumonia. RIPK3 deficiency worsens lung damage and mortality, highlighting its essential role in host defense against this common bacterial pneumonia.

Area of Science:

  • Immunology
  • Cell Biology
  • Infectious Diseases

Background:

  • Community-acquired pneumonia (CAP) is a major global health concern, with *Streptococcus pneumoniae* being a primary bacterial cause.
  • Receptor-interacting protein kinase 3 (RIPK3) is a known regulator of inflammation and cell death pathways.
  • The specific role of RIPK3 in the context of pneumococcal pneumonia remains largely unexplored.

Purpose of the Study:

  • To investigate the role of RIPK3 in host defense against *Streptococcus pneumoniae* infection.
  • To determine if RIPK3 can serve as a diagnostic marker for pneumococcal pneumonia.

Main Methods:

  • Analysis of RIPK3 protein levels in plasma from human patients with streptococcal pneumonia and healthy controls.
  • Utilized a murine model of *Streptococcus pneumoniae* pneumonia to assess the impact of RIPK3 deficiency.
  • Investigated molecular mechanisms involving RIPK3, RIPK1, MLKL, MCU, mROS, and the NLRP3 inflammasome in macrophages.

Main Results:

  • Elevated RIPK3 protein concentrations were observed in patients with pneumococcal pneumonia, suggesting its potential as a plasma biomarker.
  • RIPK3-deficient mice exhibited impaired bacterial clearance, increased lung pathology, and significantly higher mortality rates.
  • RIPK3 was found to complex with RIPK1, MLKL, and MCU, promoting mitochondrial calcium uptake and mROS production, crucial for activating necroptosis and the NLRP3 inflammasome via the mROS-AKT pathway.

Conclusions:

  • RIPK3 plays a critical role in host defense against *Streptococcus pneumoniae* infection.
  • RIPK3-mediated necroptosis is essential for controlling pneumococcal pneumonia by initiating mROS production and NLRP3 inflammasome activation.
  • RIPK3 represents a potential therapeutic target and diagnostic marker for pneumococcal pneumonia.
Keywords:
Streptococcus pneumoniaemitochondrial permeability transition porepneumoniareceptor-interacting protein kinase 3

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