Introduction

What is ageusia? This is the condition of complete taste loss.¹ Any damage to cranial nerves (CN) VII, IX, and X of your brain leads to functional disruption within the regions of the forebrain, like the thalamus and amygdala.² This ultimately causes gustatory problems

Whenever we talk about the prevalence of ageusia, Rathee and the team reported that 1 in a thousand people are the victims of this taste dysfunction.¹ f you get an infection, it can affect your taste buds and lead to ageusia. In this article, we will discuss how infections and inflammation play a role in this process.

How do we taste foods?

Taste buds are present in the papillae of the tongue.¹ Taste mechanism processes through the following cells present within taste buds:^1,3

• Type I for salty taste
• G-protein coupled receptors (GPCRs) to detect sweet, umami and bitter tastes
• Type-III to detect sour 

Normally, taste cell receptors (TCRs) sense food flavours (like salt) and then convey such chemical stimuli to the neuronal network (sensory) present within TCRs. In it, chemical signals are transduced into electrical signals and are sent to the brain through CN. This will make the person decide either to ingest or spit out the food depending on its palatability.^2,3

Which factors lead to taste dysfunction?

Multiple factors impair the physiological functions of chemical-sensing proteins (taste buds). These include:^4,5

• Medicines like atropine and bronchodilators
• Viral infections like coronavirus 
• Radiation
• Allergic rhinitis
• Pregnancy and menopause in women
• Obesity
• Zinc deficiency 
• Schizophrenia
• Dental problems 
• Aging
• Injury to the head
• Surgical operations (e.g. for cancer)

How does taste dysfunction occur?

Infection in the oral mucosa triggers the inflammatory pathways, which damage the afferent nerve fibres (CN) responsible for the perception of taste.^1,6 In addition to this, a reduction in the number of taste buds in chemotherapeutic patients or patients undergoing cancer therapy and loss of regenerative ability in aged persons impairs taste sensation.¹ Hormonal shifts also influence the tasting ability in menopausal and pregnant women. Besides, obese patients are more likely to produce the inflammatory interleukins (IL) and tumour necrosis factor alpha (TNF-𝛼) according to the studies conducted by Andrew Kaufman.⁴ Zinc deficiency impairs the regenerative ability of taste buds and reduces gustin, leading to taste dysfunction.¹

How does infection lead to inflammatory action in ageusia?

Viral and bacterial invasion of mucosal surfaces stimulates Toll-like receptors (TLR) (proteins on taste buds that detect pathogens) present on the taste buds. 

What type of stimulus activates TLR?

Exogenous pathogen-associated molecular patterns (PAMPS) (parts of viruses or bacteria that alert the immune system) include viral and bacterial cell wall components. For example, lipoproteins, flagellins, and lipopolysaccharides (LPS) are different bacterial structures and result in damage-associated molecular patterns (DAMPS) (molecules released from injured cells) like lactoferrin (peptides), amyloids (fatty acids), and biglycans (proteoglycans).⁸

How does COVID-19 cause taste loss? 

SARS-CoV-2 binds to angiotensin-converting enzyme (ACE-2) receptors (entry points on taste cells) present in type II TCRS (taste receptor cells that detect sweet, umami, and bitter flavours) within the papillary region. Such interaction with COVID-19 entry receptors facilitates the viral entry into taste cells directly, where TLRs are also coexpressed.⁹

Inflammatory mechanisms behind ageusia

TLR response to infections

TLRs are present in taste bud cells, type II. Activation of TLRs releases pro-inflammatory chemicals (substances that cause inflammation) like interferons (IFN), chemokines, and interleukins (IL), which result in inflammation.^7,8,10,11,12

How are inflammatory chemicals linked to ageusia?

Interferon acts through IFN receptors (IFNR Type I and II) (proteins on taste cells that detect interferon signals), which are expressed in NCAM (cell adhesion molecule) and G-protein α-gustducin-expressing type II and III cells (types of taste cells that sense flavours). This transduces endogenous interferon signals through the Janus kinases signal transducer and activator of transcription (JAK-STAT) pathway  (chain of signals inside the cell that controls gene activity) and results in the apoptosis (programmed cell death) of TCRS and taste buds through the release of the following pro-apoptotic proteins (proteins that trigger cell death).¹⁰

• Cysteine aspartic proteases (CASPASES) or enzymes that break down cell components
• Bax (B cell lymphoma-2-associated X protein) or protein that promotes cell death
• P27 (protein that stops cell growth)
• Fas Ligand (protein that signals cells to die)
• CD95 (cell surface protein that triggers apoptosis)

In addition to this, IFN reduces the expression of the c-fos gene (a protein on the cell surface that causes apoptosis), which is important for the renewal and differentiation of taste cells.¹² In this way, the normal functioning of taste buds and the renewal mechanism of TCRS are lost, resulting in the loss of taste sensations.¹⁰

Role of TNF in Taste Cell Inflammation

TNF markers (proteins that promote inflammation) may act as a ligand for TNF receptors (TNF-detecting proteins) present in type II taste cells, where these play a role in inflammation through the nuclear factor kappa-B (NF-kB) pathway (a signalling system that activates genes linked to inflammation), culminating in further transcription of the same inflammatory genes, like cyclooxygenases (COX) (enzymes that produce compounds that cause inflammation), TNF, IL, neutrophil activating proteins, and inducible nitric oxide (iNOS) (molecule that contributes to inflammation).¹¹

Consequently, inflammation and infection recruit more immune cells like macrophages and neutrophils to the infected area, which engulf and destroy the injurious agents and release more pro-inflammatory and apoptotic markers in that area.¹³

Summary

Ageusia is the complete loss of taste. The tongue possesses taste buds, which serve as chemosensory regions and contain different types of cells having receptors for both sensing food flavours and for immunity. When a virus, bacteria or fungi invade your oral cavity, specifically the tongue area, then it is termed an oral infection. This further triggers inflammatory mechanisms through TCRs (TLR,  IFNR and TNFR) and results in apoptosis, inflammation, and loss of regenerative capacity of taste buds. Such activity impairs the functionality of taste cells, leading to complete taste loss.

FAQs

Which brain disorders cause ageusia?

Alzheimer's disease (AD), dementia, head injury, major depression and epileptic attacks may cause complete taste loss.¹² 

Do only viral infections disrupt the function of taste cells?

No, every type of infection results in ageusia.

For example: 

• Bacterial (sinusitis)
• Viral (cold) 
• Fungal infections (candidiasis)

Which cranial nerves control taste?

Cranial nerves VII, IX and X are involved in taste sensation.²

Name the autoimmune disease responsible for taste disorders.

Sjögren's syndrome (SS) is a crucial factor in causing ageusia. Others may include systemic lupus erythematosus (SLE).

Is ageusia related to SS?

Yes, SS leads to ageusia because SS is an autoimmune disorder in which inflammation of the salivary glands occurs. This will cause destruction of nearby taste buds too and resultantly impair the function of taste cell receptors.