You spot a spreading black stain on the wall of your bathroom behind the cabinet. Finally, you’ve found the source of your sneezing, runny nose and itchy eyes: mould. But you remember a time when you didn’t have these symptoms. What has changed?

About mould allergy

Mould can grow in many places – outdoors under piles of cut leaves or in compost, and indoors on rotting food, in corners, near window frames, and on fridge seals, among other places. Although mould thrives in damp, poorly ventilated environments, it is present practically everywhere, and we come into contact with it daily. Its presence often goes unnoticed, but around 5 to 20% of the population could develop allergic reactions to mould.¹

Symptoms of mould allergy, such as a runny nose and itchy eyes, can occur throughout the year, but can be worse in damp, rainy seasons, in autumn and winter. Those at highest risk are babies, children and the elderly, and people with respiratory problems (asthma or other allergies), or weakened immune systems. Risk can also increase if there is a family history of mould allergy, exposure to a damp environment due to their profession (like farming, or winemaking) or those living in conditions with high humidity and poor ventilation. If a person develops sensitivity to mould, their immune system behaves differently from others’. But how?

How does mould trigger an allergic reaction?

When mould releases its spores, they are carried away in the air, a simple mode of spread. But the spores can be inhaled by humans through their nose or mouth and enter their body. In most instances, a healthy person’s body won't react, but there are instances where people do. In response to the mould inhalation and exposure, their body creates an allergic reaction. But what is an allergy, and how does it develop?

Allergies and their main contributors

The immune system’s role is to identify and neutralise potential threats to the body, but sometimes it malfunctions. An allergic reaction is an exaggerated natural reaction to harmless substances (called allergens), which are identified as harmful by the immune system. It is a complex cascade starting with a single mould spore entering the body and eventually leading to symptoms such as a runny nose, sneezing and itchy eyes. Numerous participants are involved in the process.

There are six types of immune system cells that play crucial roles:

• Dendritic cell: located on surfaces of tissues that are in contact with the outer environment (e.g. skin, lung, nasal membrane, gut tracts), with a main duty to present harmful substances to other immune cells
• T helper cell: a type of lymphocyte that does not directly kill bacteria or viruses, but instructs other cells to target and eliminate foreign substances 
• B cell: also belongs to lymphocytes and fights against foreign substances with specialised proteins, called antibodies
• Mast cell: does not directly fight foreign substances, but prepares the immune response for other cells by dilating blood vessels that help these other cells to migrate 
• Basophil: a type of granulocyte which releases chemical compounds to improve blood flow in injured tissue and prevent blood clots
• Eosinophil: another granulocyte that releases toxic proteins that can destroy and consume foreign substances 

Let’s see, step-by-step, how these cells behave in an allergic reaction.

Sensitisation (initial phase)

When mould spores enter the respiratory system, they can come into contact with dendritic cells. After this encounter, these dendritic cells activate, break down the spores into smaller fragments and attach them to their surface. With these fragments on their surface, the dendritic cells start to migrate to the lymph nodes.

Lymph nodes are bean-sized structures that act as filters for harmful substances and provide shelter to immune cells, such as T cells. When the dendritic cells arrive in the lymph nodes, they present the mould fragments to the naive T helper (Th0) cells. They are called naive due to their lack of differentiation. These cells are in a phase where they are waiting for a signal to arrive, so they can differentiate further with a purpose and a duty to fulfil. In this case, the Th0 cells turn into T helper 2 (Th2) cells, which have received the signal to activate other cells against the mould fragments.

Initially, the Th2 cells begin to release cytokines, which act as chemical messengers between cells. Interleukins belong to cytokines and facilitate the signalling between immune cells. One of these is called interleukin-4 (IL-4), which is released in large numbers by activated Th2 cells. 

In the lymph nodes, B cells are also located, waiting again for a signal. This signal is a combination of IL-4 that binds to the cell’s surface and the presence of Th2. It creates the message for the B cells to produce antibodies against the mould. By following this signal, the B cells produce mould-specific immunoglobulin E (IgE) antibodies, which are released in large numbers into the bloodstream. They circulate in the body and bind to the surface of mast cells in tissues, and onto basophils in the blood. This process does not necessarily cause any symptoms yet, but the immune system is now sensitised and ready to fight.²

But what happens after another exposure?

The process of sensitisation (Created using https://BioRender.com)

Elicitation (effector) phase

As many as ten thousand IgE molecules are situated on the surfaces of mast cells, waiting for another set of mould allergens. When this sensitised immune system encounters mould spores again, these mould-specific IgE molecules start binding the mould fragments. After enough IgE has bound to mould fragments, collectively, they begin to occupy too much space, aggregating and being physically brought together. These aggregating complexes serve as a signal, resulting in the activation of mast cells via a process called mast cell degranulation.

As the walls of mast cells are permeable, they can allow the movement of substances between the intracellular and extracellular environments. When the mast cells are activated, their walls increase in permeability, allowing for the release of granules. These granules are filled with mediators, known as chemical messengers. These chemical messengers drive the symptoms and processes of inflammation and allergy.

Within seconds or minutes of the re-exposure, the mast cell releases granules with previously formed mediators, such as histamine, tryptase and chymase.

• Histamine: makes the blood vessels dilate and leak fluids, which leads to swelling, redness, a runny nose and itching
• Tryptase and chymase: they play a crucial role in the remodelling of damaged tissue, and they promote the inflammation further by activating more immune cells and strengthening the allergic response^3,4

Besides the immediate reaction, lasting minutes to hours, the mast cells produce on-demand mediators:

• Leukotrienes: cause prolonged tightening of airways and increase mucus production, which are the major contributors to asthma symptoms⁵
• Prostaglandin D2: causes widening of blood vessels and more mucus secretion, which worsens nasal congestion and asthma⁶
• Cytokines (e.g. IL-4 and IL-5): signals to other immune cells, which sustain chronic inflammation

Mast cells are not the only cells that are activated during this phase. Basophils circulating in the bloodstream are also able to bind IgE molecules and degranulate. In addition to IL-4, they release histamine and other mediators, which promote Th2 activation and further IgE production. These processes amplify the allergic response and are crucial for the development of later symptoms.

Eosinophils are a key component of late-phase allergic reactions. In the elicitation phase, Th2 cells start to release interleukins as well, such as interleukin-5 (IL-5). This messenger molecule is crucial in the activation of eosinophils. After their activation, they release toxic granules that cause damage to the airway surfaces, contributing to tissue inflammation and prolonging the allergic reaction.²

The process of elicitation (Created using https://BioRender.com)

What are the symptoms of mould allergy? 

Minutes after the exposure to mould spores, the mast cells in the respiratory tract quickly degranulate. The released histamine and other mediators cause the first typical symptoms of mould allergy, such as sneezing, runny nose and nasal itching. Besides the nasal symptoms, wheezing, coughing, and chest tightness can also be present. The mast cells in the eye cause irritation and itchy, watery eyes. If someone gets in contact with mould spores via their skin, it can lead to itchiness and rashes.

Hours following the exposure, the immune cells (such as Th2 cells, eosinophils and basophils) migrate into the respiratory tissues and cause sustained inflammation and tissue damage. This causes nasal congestion, coughing, and worsening asthma symptoms, which are relieved only hours or days later.

However, if someone is continuously or frequently exposed to mould, allergens will keep activating the Th2 cells and eosinophils. The result is a chronic inflammation, with thickening of airway walls and increased mucus gland size, airway hyperresponsiveness (when even a mild irritant will cause overreaction) and persistent symptoms, such as chronic nasal congestion and frequent asthma attacks.²

Summary

Mould allergy can affect 1 out of 5 people, causing a runny nose, sneezing, and coughing, as well as itchy, irritated, red eyes. Understanding the mechanism of this allergic reaction can help to ease the symptoms and prevent long-term effects.

When mould spores are inhaled, the first phase is called sensitisation, when the immune system prepares the body for the next exposure to mould by creating allergen-specific IgE antibodies. In the elicitation phase, the immune system cells falsely attack the allergen, which leads to the symptoms that people with mould allergy often experience. 

FAQs

Why is someone more tolerant of mould than I am?

It is suggested that mould allergy develops in people who have certain genetic factors that are associated with higher IgE production.^7,8 It is shown that growing up in a highly polluted environment or getting exposed to viral infections in the early years can increase the risk of allergies.⁹ People with less genetic susceptibility and a more protective environment (like a varied microbial exposure as a child) are less likely to develop allergies.¹⁰

What happens differently in the cells when someone is not allergic to mould?

When a healthy individual inhales mould spores, the dendritic cells still present mould allergens to the Th0 cells, but then the cascade is different. Instead of differentiating into Th2, Th0 cells differentiate into regulatory T (Treg) cells. They release different cytokines (interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β)) with the main duty to suppress the excessive immune reaction and encourage tolerance against the mould allergens.¹¹

How do medicines work against mould allergy?

Antihistamines are one of the most well-known drugs against allergy symptoms. They block the release of histamine from cells, preventing itching, swelling and a runny nose. Corticosteroids suppress the production of the previously mentioned cytokines (such as IL-4 and IL-5) and are therefore able to reduce chronic inflammation. Certain medicines, like mast cell stabilisers, prevent mast cell degranulation, while others block leukotrienes and provide relief to the asthmatic airways.