Candida albicans phospholipomannan is sensed through toll-like receptors

Thierry Jouault1, Stella Ibata-Ombetta, Osamu Takeuchi

  • 1Laboratoire de Mycologie Fondamentale et Appliquée, Inserm EMI0360, Université de Lille II, Lille, France. tjouault@univ-lille2.fr

Insights

Candida albicans phospholipomannan (PLM) triggers immune responses. Toll-like receptor 2 (TLR2) is crucial for this recognition, highlighting PLM as a potential pathogen-associated molecular pattern.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Candida albicans is a commensal yeast that can cause severe infections in immunocompromised individuals.
  • The yeast cell surface features phospholipomannan (PLM), a glycolipid implicated in immune stimulation.
  • PLM induces tumor necrosis factor-alpha (TNF-alpha) production, linked to nuclear factor-kappaB (NF-kappaB) activation.

Purpose of the Study:

  • To investigate the role of Toll-like receptors (TLRs) in mediating the immune response to C. albicans phospholipomannan (PLM).

Main Methods:

  • Utilized J774 mouse cells with gene deletions for TLR4, TLR6, and TLR2.
  • Incubated these cells with PLM to assess TNF-alpha production.
  • Analyzed the impact of TLR gene deletions on PLM-induced immune cell activation.

Main Results:

  • Wild-type cells showed significant TNF-alpha production upon PLM stimulation.
  • Deletion of TLR4 and TLR6 genes resulted in minor changes in the PLM response.
  • Complete abolition of the cellular response was observed in cells lacking the TLR2 gene.

Conclusions:

  • Toll-like receptor 2 (TLR2) is essential for recognizing Candida albicans phospholipomannan (PLM).
  • PLM recognition by TLRs suggests its role as a pathogen-associated molecular pattern (PAMP).
  • This finding contributes to understanding C. albicans pathogenesis and immune evasion strategies.

Related Concept Videos

Candidiasis01:20

Candidiasis

Candidiasis is a fungal infection caused by opportunistic species of Candida. It can affect various anatomical sites, including the skin, oral cavity, nails, and genitourinary tract. Among its forms, vaginal candidiasis is the most common type of mucosal infection. It typically results from the overgrowth of Candida albicans in the vaginal mucosa. Under normal conditions, C. albicans exists as a commensal organism within the vaginal microbiota, regulated by the dominance of lactobacilli, which...
Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...
Yeast Signaling01:41

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...