Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus

Related Experiment Video

Updated: Sep 30, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

Salamatu S Mambula1, Keya Sau, Philipp Henneke

  • 1Evans Memorial Department of Clinical Research, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

The Journal of Biological Chemistry
|August 13, 2002
PubMed

Insights

Toll-like receptor (TLR)-2 and MyD88 are crucial for immune responses to Aspergillus fumigatus. While TLR-2 is vital in both mouse and human cells, CD14 plays a role only in human cells for fungal recognition.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Aspergillus fumigatus infections pose severe risks to immunocompromised individuals.
  • Phagocytic cell defects impair the body's defense against fungal pathogens.
  • Understanding innate immune recognition of A. fumigatus is critical for developing treatments.

Purpose of the Study:

  • To investigate the roles of Toll-like receptor (TLR)-2, TLR4, MyD88, and CD14 in cellular responses to different forms of Aspergillus fumigatus.
  • To elucidate the signaling pathways involved in recognizing resting conidia, swollen conidia, and hyphae.

Main Methods:

  • Utilized knockout mouse macrophages (TLR2-/-, TLR4-/-, MyD88-/-, CD14-/-) and wild-type controls.
  • Assessed tumor necrosis factor-alpha (TNFα) production and cellular binding of A. fumigatus forms.
  • Employed reporter gene assays in human cell lines (THP-1, HEK293) to measure nuclear factor kappa B (NFκB) activation.

Main Results:

  • TLR2(-/-) and MyD88(-/-) macrophages showed reduced TNFα production upon A. fumigatus stimulation.
  • TLR4(-/-) and CD14(-/-) macrophages did not exhibit defects in TNFα release.
  • NFκB activation and TNFα release were enhanced in human CD14-transfected cells and TLR2-transfected HEK293 cells, with co-transfection of TLR2 and CD14 yielding the highest activity.

Conclusions:

  • Optimal innate immune signaling against Aspergillus fumigatus requires TLR2 in both murine and human cells.
  • CD14 is essential for A. fumigatus recognition specifically in human cells.
  • MyD88 functions as a key adapter protein mediating downstream signaling pathways in response to A. fumigatus.

More Related Videos

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF107:42

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1

Published on: February 28, 2025

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Cell Signaling in Plants01:25

Cell Signaling in Plants

Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
Acute Inflammation I: Inflammatory Response01:26

Acute Inflammation I: Inflammatory Response

Acute inflammation is a rapid, short-lived physiological response to tissue injury or infection, designed to eliminate harmful agents and initiate repair. This tightly regulated process typically lasts from minutes to several days and is triggered by factors such as microbial invasion, physical trauma, or chemical injury.Recognition and Mediator ReleaseThe inflammatory response begins when resident immune cells—such as mast cells, macrophages, and dendritic cells—detect damage-associated...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Fungal Phylum Ascomycota01:28

Fungal Phylum Ascomycota

Phylum Ascomycota, a major division within the subkingdom Dikarya, comprises a diverse range of fungal species, including both unicellular yeasts and filamentous molds such as Aspergillus and Penicillium. These fungi thrive in a variety of habitats, from aquatic ecosystems to terrestrial environments, playing crucial ecological and economic roles.Morphology and ReproductionThe defining characteristic of Ascomycetes, commonly referred to as sac fungi, is the ascus—a sac-like structure that...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...