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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Bacterial pathogens activate a common inflammatory pathway through IFNλ regulation of PDCD4

Taylor S Cohen1, Alice S Prince

  • 1Department of Pediatrics, Columbia University, New York, New York, United States of America.

Plos Pathogens
|October 8, 2013
PubMed

Insights

Type III interferons (IFNλ) promote inflammation during bacterial pneumonia by inhibiting miR-21, leading to increased PDCD4. This pathway exacerbates lung pathology and impairs bacterial clearance in mice.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Microbiology

Background:

  • Type III interferons (IFNλ) and their receptor IL-28R are crucial for antiviral defense in the respiratory tract.
  • The role of IFNλ in bacterial infections, particularly in the lungs, remains largely unexplored.

Purpose of the Study:

  • To investigate the role of the IFNλ pathway in the innate immune response to bacterial lung infections.
  • To elucidate the molecular mechanisms by which IFNλ influences inflammation and bacterial clearance.

Main Methods:

  • Utilized IL-28R null mice and wild-type controls infected with Staphylococcus aureus and Pseudomonas aeruginosa.
  • Analyzed bacterial load, lung pathology, cytokine profiles, and molecular changes including miR-21 and PDCD4 expression.
  • Employed PDCD4 null mice to assess the functional significance of PDCD4 in bacterial pneumonia.

Main Results:

  • IFNλ was induced by S. aureus and P. aeruginosa in the lungs.
  • IL-28R null mice exhibited enhanced bacterial clearance, reduced lung pathology, and altered cytokine balance compared to controls.
  • IFNλ was found to inhibit miR-21 via STAT3, upregulating PDCD4, which promotes inflammation. PDCD4 null mice showed improved outcomes after infection.

Conclusions:

  • The IFNλ-IL-28R axis promotes inflammation during bacterial pneumonia by suppressing miR-21 and upregulating PDCD4.
  • Targeting this pathway may offer therapeutic strategies for bacterial lung infections.

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