Related Experiment Video

Updated: Apr 10, 2026

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay
06:15

Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay

Published on: September 7, 2018

10.0K

TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Mediates Antibacterial Defense during Gram-Negative

Miriam H P van Lieshout1, Sandrine Florquin, Cornelis Vanʼt Veer

  • 1Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Journal of Innate Immunity
|June 13, 2015
PubMed

Insights

TIR-domain-containing adaptor-inducing interferon-β (TRIF) is crucial for controlling Klebsiella pneumoniae infections. TRIF deficiency impairs antibacterial defense by reducing interferon-gamma (IFN-γ) production, leading to increased bacterial spread.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Klebsiella pneumoniae is a significant pathogen causing Gram-negative pneumonia and sepsis.
  • Mice lacking TIR-domain-containing adaptor-inducing interferon-β (TRIF) exhibit heightened bacterial proliferation and dissemination during K. pneumoniae infection.

Purpose of the Study:

  • To investigate the role of TRIF in the host immune response to Klebsiella pneumoniae pneumonia.
  • To elucidate the mechanisms underlying the impaired antibacterial defense in TRIF-deficient mice.

Main Methods:

  • Utilized TRIF-deficient mice to model Klebsiella pneumoniae pneumonia.
  • Assessed bacterial loads, cytokine production (specifically interferon-gamma), and hepatocellular injury.
  • Investigated the dependency of interferon-gamma production on Toll-like receptor 4 (TLR4), MyD88, and TRIF in vitro.
  • Administered recombinant interferon-gamma to TRIF-deficient mice to evaluate its therapeutic potential.

Main Results:

  • TRIF-deficient mice showed absent interferon-gamma production in the lungs during K. pneumoniae infection.
  • Interferon-gamma production by splenocytes was dependent on TLR4, MyD88, and TRIF.
  • Airway administration of interferon-gamma to TRIF-deficient mice reduced bacterial loads and partially restored pulmonary cytokine levels.
  • The enhanced antibacterial response in TRIF-deficient mice treated with interferon-gamma was associated with increased hepatocellular injury.

Conclusions:

  • TRIF plays a critical role in mediating antibacterial defense against Gram-negative pneumonia, partly through inducing interferon-gamma at the infection site.
  • Interferon-gamma induction is a key pathway regulated by TRIF in response to Klebsiella pneumoniae.
  • Targeting the TRIF-interferon-gamma axis may offer therapeutic strategies for Gram-negative pneumonia, while considering potential side effects like liver injury.

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

12.6K
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages08:34

Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages

Published on: February 22, 2017

12.1K

Related Concept Videos

Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
15.4K
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
912
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
3.6K
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
34
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
100
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
132