Related Experiment Video

Updated: Jul 3, 2026

Flow Cytometric Measurement Of ROS Production In Macrophages In Response To FcγR Cross-linking
13:20

Flow Cytometric Measurement Of ROS Production In Macrophages In Response To FcγR Cross-linking

Published on: March 7, 2019

Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase

Robert Paul1, Bianca Obermaier, Jessica Van Ziffle

  • 1Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, D-81377 Munich, Germany. robert.paul@med.uni-muenchen.de

Journal of Leukocyte Biology
|July 16, 2008
PubMed

Insights

Myeloid Src family kinases (SFKs) are crucial for clearing pneumococcal meningitis by controlling neutrophil function. Mice lacking these kinases showed impaired bacterial clearance and worse outcomes, highlighting their role in innate immunity.

Area of Science:

  • Immunology
  • Neuroscience
  • Cell Biology

Background:

  • Myeloid cells, including neutrophils and macrophages, are vital for innate immunity against bacterial infections.
  • Myeloid Src family kinases (SFKs) like Hck, Fgr, and Lyn regulate key leukocyte functions, including integrin signaling and phagocytosis.
  • Pneumococcal meningitis is a serious central nervous system (CNS) infection requiring effective immune responses.

Purpose of the Study:

  • To investigate the role of myeloid SFKs in host defense during pneumococcal meningitis.
  • To determine the impact of myeloid SFK deficiency on leukocyte recruitment, bacterial clearance, and clinical outcomes.
  • To elucidate the mechanisms by which myeloid SFKs and complement receptor 3 (CR3) mediate host defense in CNS infections.

Main Methods:

  • Generation and analysis of mice deficient in all three myeloid SFKs (hck(-/-)fgr(-/-)lyn(-/-)).
  • Induction of pneumococcal meningitis in wild-type and knockout mice.
  • Assessment of leukocyte recruitment into cerebrospinal fluid (CSF), bacterial load, intracranial pressure, and clinical symptoms.
  • Evaluation of neutrophil phagocytosis, superoxide production, and NADPH oxidase activation.
  • Analysis of mice lacking complement receptor 3 (CR3).

Main Results:

  • Mice lacking myeloid SFKs exhibited significantly impaired leukocyte recruitment and bacterial clearance in the CSF during pneumococcal meningitis.
  • Triple knockout mice showed increased intracranial pressure, neurological deficits, and mortality compared to wild-type controls.
  • Neutrophils from SFK-deficient mice displayed defective phagocytosis, reduced superoxide production, and impaired NADPH oxidase activation.
  • Mice lacking CR3 also showed impaired host defense and neutrophil superoxide production, but normal CSF pleocytosis.
  • Cytokine and chemokine expression in the brain was not reduced in either knockout model, indicating SFKs and CR3 are not essential for inflammatory mediator production.

Conclusions:

  • Myeloid SFKs play a critical role in host defense against Streptococcus pneumoniae CNS infection by regulating phagocytosis and NADPH oxidase-dependent superoxide production.
  • Complement receptor 3 (CR3) is also essential for effective defense against pneumococcal meningitis, particularly in neutrophil function.
  • SFKs are pivotal mediators of CR3 signal transduction in the context of host defense against CNS bacterial infections.
  • Targeting myeloid SFKs and CR3 pathways may offer therapeutic strategies for managing bacterial meningitis.

More Related Videos

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models10:42

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models

Published on: October 22, 2012

Measuring Phagosome pH by Ratiometric Fluorescence Microscopy14:39

Measuring Phagosome pH by Ratiometric Fluorescence Microscopy

Published on: December 7, 2015

Related Concept Videos

Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Bacterial Meningitis01:24

Bacterial Meningitis

Bacterial meningitis is a severe infectious disease involving inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. It occurs when pathogenic bacteria cross the blood–brain barrier and enter the cerebrospinal fluid. Common causative organisms include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, Listeria monocytogenes, and Escherichia coli K1. The exact route of entry varies by pathogen and host condition.Routes of Entry...
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...