Related Experiment Video

Updated: Jan 9, 2026

The Nematode Caenorhabditis Elegans - A Versatile In Vivo Model to Study Host-microbe Interactions
11:58

The Nematode Caenorhabditis Elegans - A Versatile In Vivo Model to Study Host-microbe Interactions

Published on: October 18, 2017

9.9K

Reactive oxygen species drive the aberrant immune response to a C. neoformans chitin synthase 3 (chs3Δ) mutant

Rebekah G Watson1, Camaron R Hole1

  • 1Department of Clinical Pharmacy and Translational Science, The University of Tennessee Health Science Center, Memphis, TN, United States.

Frontiers in Immunology
|December 8, 2025
PubMed

Insights

Heat-killed Cryptococcus neoformans lacking chitosan triggers lethal inflammation. Neutrophils cause this pathology via reactive oxygen species (ROS), not the fungi themselves, highlighting ROS

Area of Science:

  • Immunology
  • Mycology
  • Pathogen-associated molecular patterns (PAMPs)

Background:

  • Cryptococcus neoformans is a major fungal pathogen causing opportunistic infections.
  • Chitosan, a chitin derivative, modulates immune responses during C. neoformans infection.
  • Previous work showed heat-killed, chitosan-deficient C. neoformans (chs3Δ) causes rapid, neutrophil-dependent mortality.

Purpose of the Study:

  • Investigate the immune mechanisms behind the lethal inflammatory response to chs3Δ C. neoformans.
  • Assess the roles of inflammatory cytokines, adaptive immunity, and neutrophil effector functions.

Main Methods:

  • Utilized knockout mouse models: IL-6-deficient, Rag1-deficient, and NADPH oxidase 2 (NOX2)-deficient mice.
  • Compared pulmonary neutrophil recruitment and inflammatory mediator levels in wild-type versus NOX2-deficient mice.
  • Monitored survival rates and disease progression in different mouse models.

Main Results:

  • IL-6-deficient and Rag1-deficient mice showed only modest survival benefits.
  • Mice lacking NOX2, essential for reactive oxygen species (ROS) production, were completely protected from mortality.
  • Despite similar neutrophil infiltration, wild-type mice exhibited higher proinflammatory cytokine/chemokine levels and succumbed to infection.

Conclusions:

  • Neutrophils are not intrinsically pathogenic in this model but mediate lethal immunopathology.
  • Lethal inflammation is driven by ROS-dependent inflammatory amplification, not the fungi directly.
  • Phagocyte-derived ROS are critical mediators of severe inflammatory responses to C. neoformans chitin.
Keywords:
Cryptococcuschitin synthaseinflammationneutrophilreactive oxygen species

More Related Videos

Flow Cytometric Measurement Of ROS Production In Macrophages In Response To FcγR Cross-linking13:20

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

Published on: March 7, 2019

16.5K
Author Spotlight: Advancing Immune Monitoring in Critical Care Patients Using Whole Blood Assays06:03

Author Spotlight: Advancing Immune Monitoring in Critical Care Patients Using Whole Blood Assays

Published on: September 20, 2024

1.7K

Related Concept Videos

Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
4.1K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.1K
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
1.3K