• Martin Laurence

Psoriasis and Candida

Psoriasis and Candida: the problem

In 1925, Fleisher and Wachowiak discovered that psoriasis patients had high rates of Candida in their guts as compared to healthy controls (Fleisher et al 1925). Their findings were later confirmed by many research groups (Soyuer et al 1991; Waldman et al 2001). Initially they thought psoriasis was the result of Candida on the skin, but they were surprised to discover that psoriatic lesions were Candida-free! What could explain this association then?

Focal infection theory

As Fleisher and Wachowiak worked on psoriasis, many other researchers noticed a similar pattern in other diseases: an infection in one organ seemed to cause sterile inflammation elsewhere in the body. For example, bacterial infections in the mouth seemed to cause chronic eye pain, even though no bacteria could be found in the eye. Once the mouth infection cleared, the eye pain stopped. This was called the focal infection theory (Benedict 1921; Benedict et al 1926). Proponents of this theory were faced with a seemingly inexplicable phenomenon: what allowed inflammation to spread from the mouth to the eye?


In the first half of the 20th century, researchers who studied this problem thought bacterial toxins entered the bloodstream in the mouth, and reached the eye through our circulatory system. This could explain why no bacteria were present in the eye: it was bacterial toxins, not bacteria themselves, which reached the eye and caused inflammation. However, no such toxins were found despite much research effort.

Molecular mimicry

Modern research on this problem has focused on molecular mimicry as the explanatory mechanism. Lymphocytes which are fighting bacteria in the mouth accidentally decide to fight human cells instead! This means infections would cause autoimmunity by tricking our immune system to attack our own cells. It’s an attractive solution because it can explain so many observations. It’s also wrong (see the FAQ for a detailed explanation, and the reactive arthritis section below).

Reports of infections in one part of the body causing seemingly sterile inflammation in other organs keep being published, and still need to be explained. This is one of the longest standing open questions in medicine.

Reactive arthritis

Reactive arthritis is an acute type of spondyloarthritis. It is the most studied disease where an infection triggers seemingly sterile inflammation in remote organs: reactive arthritis is the poster child of focal infection theory!

The most potent microbe which can trigger reactive arthritis is Mycobacteria, the bacterium which causes tuberculosis. In 1956, Pearson developed a rat model of reactive arthritis triggered by Mycobacteria (Pearson 1956; Pearson et al 1959). He injected dead Mycobacteria into the foot, and rats developed reactive arthritis symptoms as a result: urethritis, arthritis, uveitis and psoriasis. He could repeatedly trigger inflammation in organs as far away from the foot as the eye!

Because Mycobacteria were killed before the injection, these rats did not catch tuberculosis: their symptoms could not be due to an active Mycobacteria infection. It was soon discovered that the part of the rat immune system responsible for spreading inflammation from the foot to other organs was lymphocytes (specifically αβ T cells). These T cells recognize proteins, so molecular mimicry between Mycobacteria proteins and rat proteins was initially suspected of causing autoimmunity.

Strangely, injecting Mycobacteria lipids or sugars (but not Mycobacteria proteins) causes the disease. This made no sense! If molecular mimicry between Mycobacteria proteins and rat proteins was causing autoimmunity, then eliminating Mycobacteria proteins from the injection should have prevented it. It did not. Molecular mimicry cannot explain this animal model at all! So what’s the reactive arthritis mechanism then? After 60 years of research, this remains unexplained.

As observed in rats, humans exposed to Mycobacteria are much more likely to develop reactive arthritis (Bernini et al 2013; Taniguchi et al 2017; Cheung et al 2018; Sampaio et al 2017; Kroot et al 2006; Lugo-Zamudio et al 2010). This means Pearson’s rat model of reactive arthritis probably matches reactive arthritis in humans.

Mincle and tuberculosis

Mincle is a receptor on human and rat phagocytes which recognizes an abundant Mycobacteria surface antigen called cord factor. Mincle is usually not expressed, which means phagocytes are typically not on the look-out for Mycobacteria. When the body suspects it might have tuberculosis, phagocytes express Mincle on their surface, and go around gobbling-up Mycobacteria. Eventually, the immune system manages to kill all Mycobacteria, tuberculosis ends, and phagocytes stop expressing Mincle on their surface.

Mycobacteria, Candida and Malassezia look very similar

Mycobacteria are very weird bacteria which have surface antigens similar to those of fungi. This is highly unusual: most bacterial species have surface antigens which are very different from fungi. It’s as if Mycobacteria are crossdressers who prefer looking like fungi! This means the immune response against fungi and Mycobacteria will be very similar: they look nearly identical to phagocytes.

This is particularly true for Malassezia, which shares two abundant surface antigens with Mycobacteria recognized by phagocytes: cord factor which is detected by Mincle, and mannan which is detected by Dectin-2 (Ishikawa et al 2013). Other fungal species only share one abundant surface antigen with Mycobacteria: mannan. It’s as if Mycobacteria are disguising themselves as Malassezia!

Mincle and Dectin-2 are essential to produce reactive arthritis. This makes sense because reactive arthritis can be triggered by injecting cord factor or mannan into rats, which bind to and stimulate Mincle and Dectin-2 on phagocytes. Can you guess the complete mechanism now?

Mycobacteria coax phagocytes to gobble-up Malassezia!

The solution for the animal model of reactive arthritis is that Malassezia are present on the rat’s skin, and are pushed into the foot during the injection. When Mycobacteria are absent from the injection, phagocytes do not express Mincle, so Malassezia remain invisible to them.

When either cord factor or mannan is added to the injections, phagocytes think that the rat has tuberculosis, and express Mincle to gobble-up Mycobacteria. Once Mincle is expressed, phagocytes gobble-up Malassezia too, because Mincle sticks to an abundant Malassezia surface antigen (Ishikawa et al 2013). Suddenly, the rat’s immune system thinks that there is an acute Malassezia infection in the foot! In response, it sends T cells to kill Malassezia everywhere in the body. T cells recognizing Malassezia go on to cause reactive arthritis symptoms such as psoriasis.

Psoriasis and Candida: the solution

Like Mycobacteria, Candida share surface antigens with Malassezia, in particular mannan. Mannan is not present on most bacteria; Mycobacteria and Klebsiella are notable exceptions, and both can trigger spondyloarthritis symptoms in humans. When Candida are absent, Malassezia in the gut are typically ignored by our immune system. When Candida are present, the body sometimes decides to launch T cells to attack Candida. However, Malassezia are also present in the gut!

When the immune system engages Candida in the gut, it inadvertently sends T cells to fight Malassezia too! These T cells move around the body, and open other fronts anywhere Candida or Malassezia are found, including on the skin. There is usually no Candida on the skin, but Malassezia are on everyone’s skin from birth. Wherever T cells detect Malassezia on the skin, a psoriatic lesion appears.

The same mechanism applies to other microbes which are collocated with Malassezia and induce an adaptive immune response against Malassezia (especially Mycobacteria and Klebsiella in the gut). These microbes are acting as immunological adjuvants, and trigger spondyloarthritis by blowing Malassezia’s cover!


T cells attacking Malassezia on the skin can cause psoriasis. The immune system is usually smart enough to avoid sending T cells to attack Malassezia—it knows this will make us sick! When infections sharing Malassezia antigens are present (Candida, Mycobacteria, Klebsiella), sometimes a mistake is made and T cells are sent after Malassezia too.

Reactive arthritis can be triggered by many different types of microbes, which are acting as immunological adjuvants. These microbes “provoke” the immune system (they blow Malassezia’s cover), inducing an adaptive immune response against Malassezia.

Animated psoriasis video:


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