Pattern recognition molecule mindin promotes intranasal clearance of influenza viruses

Wei Jia1, Hong Li, You-Wen He

  • 1Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

Insights

Mindin, an innate immune molecule, is crucial for fighting influenza virus infections. Mindin deficiency increases viral load, while its administration enhances viral clearance, highlighting its potential as an immune therapy.

Area of Science:

  • Immunology
  • Virology
  • Biochemistry

Background:

  • The innate immune system relies on pattern recognition molecules to detect microbial pathogens.
  • Mindin, an extracellular matrix protein, previously identified as a pattern recognition molecule for bacteria.
  • The role of mindin in viral infections, specifically influenza, was not previously established.

Purpose of the Study:

  • To investigate the function of mindin in the host's innate immune response against influenza virus infection.
  • To determine if mindin interacts with influenza virus and influences macrophage activation.
  • To evaluate the therapeutic potential of mindin in influenza infection.

Main Methods:

  • Utilized mindin-deficient mice for intranasal and intratracheal influenza virus infection models.
  • Quantified influenza virus titers in the lungs and nasal cavities of infected mice.
  • Performed in vitro studies using mindin-deficient macrophages and influenza virus.
  • Assessed the effect of intranasal administration of recombinant mindin on viral clearance in wild-type mice.

Main Results:

  • Mindin-deficient mice exhibited significantly higher influenza virus titers in the nasal cavity and lungs after intranasal infection.
  • Intratracheal infection showed no significant difference in lung virus titers between wild-type and mindin-deficient mice.
  • Mindin directly interacted with influenza virus particles.
  • Mindin-deficient macrophages displayed impaired activation following influenza virus exposure in vitro.
  • Intranasal administration of recombinant mindin accelerated influenza virus clearance in wild-type mice.

Conclusions:

  • Mindin plays a critical role in the innate immune defense against influenza virus, particularly via the intranasal route.
  • Mindin's interaction with the virus and its effect on macrophage activation are key mechanisms of its antiviral activity.
  • Mindin demonstrates potential as a therapeutic agent for enhancing immune response and viral clearance in influenza infections.

Related Concept Videos

Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Influenza01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...