October 15, 2014 9:00 pm


Fungal infections, histamine intolerance, and mast cells have a crucial connection which is often overlooked as one source of histamine intolerance.

It is common to talk about mast cells as part of an allergic (even anaphylactic) reaction. But their role in allergic reactions is only a tiny part of the job of the mast cell. Another crucial role mast cells play in identifying and treating pathogens, such as bacteria, viruses, parasites, and fungi.

Mast cells reside strategically throughout the body in tissues commonly exposed to the external environment, such as the skin, airways, and the gut. There they are one of the first cells to make contact with pathogens.

For this life-saving task, the mast cells are perfectly equipped. They are heavily armed with mediators (such as histamine) that can be released upon contact with infections.

Indeed, infections are the most common underlying cause of histamine intolerance and mast cell activation I see in my practice.

histamine, mast cell activation, fungal, candida, bacteria, parasite, bacterial, viral infections


The mast cell is designed to identify pathogens. Identifying pathogens triggers the acute inflammatory mediators, which call more cells into the infected site. Histamine, for instance, increases blood flow to the damaged site and makes the vessels “leakier.” This leakiness allows the other inflammatory mediators access. There they combine forces with free radicals to “eat” the infection.



Mast cells can identify molecules on the surface of bacteria. These molecules bind to receptors on the surface of mast cells and trigger the release of inflammatory mediators, including histamine. Also, mast cells release molecules (proteases and cathelicidins) that can directly kill bacteria.


Viral Infections

When it comes to viral infections, the process is very similar. Viruses can activate mast cells via a specific cell surface receptor, which triggers the release of mediators (mainly interferon) that elicit an antiviral immune response. However, there is evidence that mast cells can also harm viral infections. One study showed that in response to respiratory viruses, mast cells could exacerbate or lead to the development of asthma.



The same principles apply to parasitic infections. Mast cells are preferentially located in tissues targeted by parasites, e.g., the skin and gut. These mast cells express receptors that identify specific parasitic components. Upon activation, mast cells release several inflammatory mediators that trigger the immune response necessary to eliminate the parasites.


Fungal Infections

Similarly to parasites, fungi enter the body via mast cell-rich organs (skin, gut, and airways). It is also known that mast cells have receptors that recognize fungi and trigger anti-fungal responses.

Mast cells produce several molecules involved in protective host responses to fungal pathogens.


Histamine Intolerance

The gastrointestinal tract and the skin have the highest mast cells. During an infection, the number of mast cells will rapidly increase in the gut. As the mast cells increase and interact with the pathogens, they release more inflammatory mediators (including histamine). If the histamine load exceeds the ability to degrade it, the result will be histamine intolerance.


Candida and Food Allergies

Studies show that if your gut is colonized with the fungus Candida, you are likely to become sensitive to food antigens (food allergy) because of the increased number of mast cells and the hyperpermeability of the gastrointestinal mucosa (which is caused by histamine release).


histamine intolerance, mast cell activation, autoimmunity, Alison Vickery, Health, Australia


It is very important to test for infections if you have histamine intolerances and food allergies. At a minimum, they can contribute to the histamine load if you have a histamine-related disease. They could also just be a significant part of the cause.

If you would like to find out more about the resolution of histamine intolerance and mast cell activation, you can do so in my Free Course, The Roadmap To Resolution.



Additional Reading

Saluja R, Metz M, Maurer M, “Role and relevance of mast cells in fungal infections,” Front Immunol. 2012 Jun 13;3:146.

Lopes, José Pedro, et al. “Opportunistic pathogen Candida albicans elicits a temporal response in primary human mast cells.” Scientific reports 5.1 (2015): 1-14.

Nieto-Patlán, Alejandro, et al. “Recognition of Candida albicans by Dectin-1 induces mast cell activation.” Immunobiology 220.9 (2015): 1093-1100.

Trevisan, Elisa, et al. “Mast cells kill Candida albicans in the extracellular environment but spare ingested fungi from death.” Inflammation 37.6 (2014): 2174-2189.

Song, Pu, et al. “Candidalysin, a Virulence Factor of Candida albicans, Stimulates Mast Cells by Mediating Cross-Talk Between Signaling Pathways Activated by the Dectin-1 Receptor and MAPKs.” Journal of Clinical Immunology (2022): 1-17.

Żelechowska, Paulina, et al. “Do mast cells contribute to the antifungal host defense?.” Cells 10.10 (2021): 2510.