Introduction
Dermatophytes are a type of fungus that like to grow on keratin, a protein found in skin, nails, and hair. A well-known example is Trichophyton rubrum, which causes common skin conditions like athlete’s foot and ringworm. These infections usually stay on the surface layers of the skin and tend to last a long time but don’t cause much redness or pain. This mild reaction happens because the fungus has ways to “turn down” the body’s immune system.
On the other hand, acne is a skin problem caused by inflammation in the oil glands and hair follicles. In acne, a harmless skin bacterium called Cutibacterium acnes can suddenly cause a big immune reaction. This leads to the red, swollen bumps we call pimples, papules, or pustules. These are basically small areas of infection where bacteria grow and the body sends in immune cells to fight back. But sometimes, this immune reaction goes overboard and damages healthy skin tissue too.
Because dermatophyte infections and acne cause such different immune responses, it’s interesting to ask: could the fungus’s ability to calm the immune system help reduce the inflammation seen in acne? Could it even help acne lesions heal faster? In this article, we’ll explore how dermatophytes interact with the immune system and compare that to how acne forms. We’ll also look at whether the fungus’s immune effects could, in theory, help control acne or improve how quickly acne wounds heal.
Immune Response and Immune Evasion in Dermatophyte Infection
When dermatophytes like Trichophyton rubrum first come into contact with the skin, they meet the body’s first line of defense — the innate immune system. Skin cells called keratinocytes are the first to notice the fungus. These cells act like security guards, using special sensors (called pattern recognition receptors) to detect parts of the fungus. Examples of these sensors include Toll-like receptors and C-type lectin receptors like Dectin-1.
Once the keratinocytes detect the fungus, they send out signals — small proteins called cytokines — to call for help. These signals include IL-1β, IL-6, TNF-α, and IL-8. These help attract immune cells like neutrophils to fight the infection. This early immune response then triggers a stronger one: immune cells like dendritic cells and macrophages take pieces of the fungus and present them to T cells in the lymph nodes, preparing the body for a more focused attack.
If this stronger immune response works well, two types of T cells — Th1 and Th17 — become active. Th1 cells release IFN-γ and TNF-α, and Th17 cells produce IL-17A and IL-22. These cytokines help the body kill the fungus. IL-17, in particular, is very important because it brings in more neutrophils and boosts production of antimicrobial substances to help clear the infection.
In short-term infections like ringworm, this immune activity creates red, scaly patches that usually clear up. However, T. rubrum often causes long-lasting infections. This is because the fungus has developed ways to weaken the immune response so it can stay on the skin without being removed.
One of the main ways T. rubrum does this is by releasing substances that calm down the immune system — especially the T cells that would normally attack it. Let’s look at the main tools it uses:
Mannan: The Immune-Dampening Molecule
T. rubrum has a cell wall that contains mannans, a type of sugar-protein (glycoprotein) that can interfere with how immune cells work. These mannans can attach to immune cells like monocytes and stop them from functioning normally. They also slow down how quickly skin cells grow and divide, which means infected skin sheds more slowly — allowing the fungus to stay longer.
Mannans can also stop T cells from multiplying, which weakens the body’s defense. Interestingly, T. rubrum produces more mannan than other fungi that cause more obvious infections, like Microsporum canis. This helps explain why T. rubrum can often cause infections that last longer but with fewer symptoms.
Fungal Metabolites (Toxins)
As T. rubrum grows and digests keratin, it creates substances called metabolites. One of these is kynurenic acid, which comes from breaking down the amino acid tryptophan. This compound has strong immune-suppressing effects. It can reduce the production of important immune signals like IL-4, IL-23, and TNF-α. It also stops Th17 cells from forming, which are critical in fighting fungi.
By lowering IL-23 and TNF-α levels, kynurenic acid reduces the Th17 immune response, helping the fungus stay on the skin. T. rubrum also makes other oily toxins, such as xanthomegnin, which can further weaken local immunity and — in serious cases — affect the body more broadly, possibly even lowering white blood cell counts.
Proteases: Enzymes That Interfere With Immunity
To feed on keratin, dermatophytes release enzymes called proteases. These enzymes not only break down keratin but can also damage the body’s immune tools — like antibodies and cytokines. By doing so, the fungus makes it harder for the immune system to fight back. This trick allows the fungus to grow with less resistance.
Shifting the Immune System Toward a Calmer State
Long-term dermatophyte infections often cause a change in the body’s immune response. Instead of keeping up a strong attack with Th1 and Th17 cells, the body starts to favor a “peaceful” approach, involving regulatory T cells (Tregs) and Th2 cells. Tregs release calming cytokines like IL-10 and TGF-β, which reduce inflammation and help the fungus survive without being cleared.
In people with stubborn T. rubrum infections, studies have found more Tregs in the blood compared to healthy people. IL-10 is especially important in this process. It stops immune cells like macrophages and dendritic cells from becoming fully active and blocks the release of inflammatory cytokines. T. rubrum seems to be very good at triggering IL-10 production, possibly through its mannans or other components. This creates a loop where the immune system stays quiet and the fungus stays put.
Figure 1 Summary
The best immune response against dermatophytes includes strong Th1 and Th17 activity — releasing cytokines like IFN-γ, TNF-α, IL-17A, and IL-22 to kill the fungus and bring in neutrophils. On the other hand, Th2-type responses (involving IL-4, IL-5, IL-13) and regulatory responses (IL-10, TGF-β from Tregs) are weaker at removing the infection.
T. rubrum pushes the immune system toward this weaker, anti-inflammatory state so it can survive longer. That’s why infections like athlete’s foot can go on for months or even years with little pain or swelling. This quieting of the immune system may also influence other skin conditions — like acne — where too much inflammation causes damage.
Immunological Mechanisms in Acne Inflammation
Acne happens when a mix of factors come together: too much oil (sebum) is made due to hormones, skin cells in the hair follicles grow and shed too quickly, and a common skin bacterium called Cutibacterium acnes (formerly Propionibacterium acnes) starts to grow too much in these clogged pores. These blocked pores, called microcomedones, create an environment low in oxygen and rich in oil — perfect for C. acnes to thrive.
As the bacteria grow, they release substances that trigger the body’s immune system. The skin cells and immune cells detect C. acnes using special receptors, like Toll-like receptor 2 (TLR2), found on cells such as keratinocytes and macrophages. When these receptors detect the bacteria, they signal the body to start an immune response.
In acne-prone skin, the levels of TLR2 and TLR4 are often higher, meaning the skin is especially ready to react to bacteria. Once activated, these receptors tell the skin to produce inflammatory signals like IL-1β, TNF-α, IL-8, and IL-12. Among these, IL-1β plays a big role — it increases the buildup of dead skin cells in the pores, helping pimples form and keeping inflammation going.
IL-8, also called CXCL8, is another important signal. It calls neutrophils (a type of immune cell) to the infected pore. When these cells arrive, they release enzymes and reactive oxygen substances to kill bacteria — but they also damage the pore wall in the process. This is why a pimple becomes swollen, red, and sometimes filled with pus — the pus is mostly dead neutrophils and bacteria.
Adaptive Immunity: T Cells Join In
Besides this early immune reaction, the body also brings in more specialized immune cells. Within just a few days of a pimple forming, CD4+ T cells and macrophages gather at the site. Among the CD4+ cells, two types are especially involved: Th1 and Th17.
Th1 cells are activated by IL-12 and release IFN-γ and TNF-α, which keep the inflammation going and activate macrophages. Th17 cells, activated by IL-6, IL-23, and TGF-β, produce IL-17A — a cytokine found in high amounts in acne lesions.
Studies of acne biopsies show that the Th17 pathway is much more active in acne skin compared to normal skin. IL-17A and its related signals (like IL-1β, IL-6, and IL-23) are all elevated. These cytokines not only bring in more neutrophils but also push skin cells to release more inflammatory and antimicrobial substances — making the inflammation worse.
This strong Th17/Th1 immune response is what causes the redness, swelling, and tenderness of inflamed acne pimples and pustules.
The Body’s Way of Calming the Inflammation
Even though acne involves strong immune activity, the body also tries to prevent this inflammation from getting out of control. Researchers have found that acne lesions contain higher levels of the anti-inflammatory cytokine IL-10 and more regulatory T cells (Tregs), which carry a protein called FOXP3. These Tregs help calm the immune response and keep the inflammation limited to one spot.
IL-10 is made by many cells — including Tregs, macrophages, and even oil-producing cells (sebocytes) — and its job is to block further immune activation. It stops macrophages and dendritic cells from releasing more inflammatory signals and slows down T cell responses.
This means the body is trying to keep the pimple contained, stopping the inflammation from spreading across the skin. If this local control didn’t happen, acne might look more like widespread skin infections (like cellulitis) rather than individual bumps.
Still, in people with severe or long-lasting acne, this system of immune control may not work well enough. Some studies suggest that Tregs may be less effective in these individuals, allowing the inflammation to go unchecked.
Wound Healing in Acne Lesions
Once the inflammation begins to calm down, the body starts healing the damaged skin. After the pus and dead cells are removed, the skin must repair the damage to the outer layers and the deeper structures, like collagen. If the inflammation lasts too long or is too strong, it can destroy tissue and lead to scarring — especially the sunken kind called atrophic scars.
For healing to go well, the immune response must shift from an inflammatory phase to a repair phase. Fibroblasts (cells that make collagen) and keratinocytes (skin cells) start to rebuild the area. Cytokines like TGF-β are important here — they encourage new collagen and help close the wound.
Interestingly, IL-17 — the same cytokine that causes inflammation — can also help with healing in some cases. It can promote blood vessel growth by triggering the release of VEGF (vascular endothelial growth factor), which is helpful for bringing nutrients and oxygen to the healing tissue. So, IL-17 can both harm and help, depending on the situation.
In acne, though, it’s generally better to calm the inflammation sooner so healing can happen properly. Treatments like retinoids and anti-inflammatory drugs try to reduce the signals that cause inflammation through TLRs, helping to bring the immune response back into balance.
Some newer treatments even look at probiotics — beneficial bacteria that can help the body produce more IL-10. Studies show that oral probiotics can raise IL-10 levels and reduce acne severity. This shows that moving the immune system toward a more calming, IL-10–based state (and reducing IL-17 and TNF-α) can help clear acne and improve healing.
Potential Interactions: Dermatophyte Immunomodulation vs. Acne Inflammation
Now that we’ve seen how Trichophyton rubrum affects the immune system and how acne forms, we can look at how these two processes might interact. The main idea here is that T. rubrum turns down certain immune responses — while acne turns them up. Because of this, it’s possible that the immune-dampening effects of the fungus might reduce acne-related inflammation.
Suppressing the Th17/IL-17 Pathway
Acne depends heavily on the immune pathway that goes from IL-23 to Th17 cells to IL-17A. This pathway helps bring neutrophils into the pore and causes the inflammation we see in pimples.
But T. rubrum makes kynurenic acid, a substance that can reduce both IL-23 and IL-17. This compound can “quiet down” immune activity by blocking IL-23 and TNF-α — both of which are key drivers of the acne inflammation process. If kynurenic acid is present in the skin — maybe in areas where someone has both acne and a mild fungal infection — it might reduce how strongly the skin reacts to C. acnes.
With less IL-17 and TNF-α, the skin might bring in fewer neutrophils and produce less inflammation. That could lead to smaller, less red pimples. Even though this is just a theory, it matches what we know: in diseases like psoriasis, blocking IL-23/IL-17 helps reduce skin inflammation. It’s possible the same could happen in acne — if done safely.
Increasing IL-10 and Boosting Regulatory Immune Cells
Chronic T. rubrum infections are known to increase IL-10 and Treg cells in the skin. Acne lesions also show some IL-10 activity as the body tries to control inflammation. If the fungus or its molecules make IL-10 levels even higher, that could further help calm acne inflammation.
For example, T. rubrum mannan might encourage monocytes (a type of immune cell) to release more IL-10. More IL-10 could mean less production of inflammatory signals in acne lesions, which might make pimples less painful and quicker to heal.
We’ve seen similar effects in other treatments: for instance, probiotics and vitamin D can boost IL-10 and help improve acne. If T. rubrum increases IL-10 in the same way, it might help the skin cool down the immune reaction in pimples. Also, by increasing Treg activity, the fungus might help turn off the immune response once the bacteria are under control. This could stop pimples from growing too large or inflamed.
Desensitizing the Skin’s Immune Sensors
There’s also a theory that the fungus could “numb” the skin’s sensors over time. When the skin is constantly exposed to certain microbes, it sometimes becomes less reactive — a bit like becoming tolerant to a repeated noise.
This kind of immune desensitization could happen with T. rubrum as well. Since the fungus often activates receptors like TLR2, it’s possible that the cells become less sensitive to future triggers. If C. acnes comes along later and tries to activate the same receptors, the skin might not respond as strongly.
In practical terms, if T. rubrum has already calmed down the immune sensors in one area, C. acnes might cause a weaker reaction — leading to less inflammation and a milder pimple. This idea is still theoretical, but we’ve seen similar effects in chronic viral or parasite infections, which can change how the immune system reacts to other microbes.
So, T. rubrum might be training the skin’s immune system to be less reactive — which could, by accident, help with acne flares.
Microbial Interactions Between Fungus and Bacteria
Even though T. rubrum and C. acnes live in different parts of the skin (the fungus stays on the surface while the bacteria live inside pores), their presence might still affect each other.
For example, T. rubrum might change the skin’s pH or cause the skin to produce antimicrobial peptides (AMPs) — small molecules that fight off microbes. These AMPs could help reduce the number of C. acnes bacteria. And fewer bacteria would mean less inflammation.
Some fungi produce antibacterial substances naturally. Although T. rubrum isn’t known to kill C. acnes directly, it may trigger the body to release more AMPs, which might keep the bacteria in check. This shows how different microbes can interact — not by fighting directly, but by influencing the environment they live in.
Insights from Therapeutic Experiments
Interestingly, scientists have already tested T. rubrum antigens (non-living parts of the fungus) in medical research. In one experiment involving rats with joint infections (septic arthritis caused by Staphylococcus aureus), researchers used T. rubrum culture fluid as a treatment. The rats treated with fungal antigens had less swelling and joint damage than those who weren’t.
This result suggests that T. rubrum components can reduce strong inflammation in the body. If similar molecules were present during acne breakouts, they might help lower the skin’s reaction to C. acnes. Though the exact process in that study wasn’t fully explained, it likely involved IL-10 or other calming immune pathways. The treated rats had fewer neutrophils and less tissue destruction — which supports the idea that fungal antigens have anti-inflammatory power.
In an acne setting, that could mean faster healing and smaller pimples — working much like anti-inflammatory medications. Overall, T. rubrum might help reduce acne inflammation by lowering IL-17 and TNF-α, raising IL-10, and guiding immune cells into a calmer mode.
Implications for Acne Lesion Healing
So far, we’ve looked at how dermatophytes like Trichophyton rubrum might affect how acne forms. But what about what happens after — during the healing process? Once a pimple bursts, drains, or fades, the skin starts working to fix the damage. This phase is important because how the skin heals can determine whether a scar forms — and how bad that scar might be.
Too much inflammation during healing can slow things down or even make the skin damage worse. On the other hand, if the immune response is too weak, bacteria might stick around and cause infection. The body needs just the right balance to heal properly.
Here’s where T. rubrum might play a surprising role. Its immune-dampening effects could possibly shift the skin’s environment to a more balanced, repair-friendly state.
Reducing Tissue Damage and Preventing Scars
If T. rubrum helps lower levels of inflammatory cytokines like TNF-α, IL-1β, and the harmful enzymes released by neutrophils, then less damage might occur in the acne lesion. These signals, when too high, can destroy healthy collagen and harm fibroblasts — the cells responsible for building new skin. They also increase MMPs (matrix metalloproteinases), which break down the skin’s support structures.
By calming down these signals, T. rubrum might allow the skin to keep more of its collagen and structure intact, which could result in fewer deep scars.
Also, more IL-10 in the area (thanks to the fungus’s immune influence) may push macrophages — a type of immune cell — into their healing mode (called the M2 type). These “healer” macrophages help rebuild tissue instead of breaking it down. Along with TGF-β, IL-10 encourages wound closure and repair.
This shift toward a calm, healing environment could help pimples heal faster and more cleanly — and reduce the chance of noticeable scarring.
Helping Skin Regrow with IL-22
Some cytokines triggered by T. rubrum might also directly help skin cells regrow. For example, when skin cells are exposed to the fungus, they can start producing IL-22 — a cytokine that encourages skin cell growth and movement. IL-22 plays a big role in re-covering wounds by helping keratinocytes (the main skin cells) move into the damaged area.
Even though IL-22 is sometimes linked to overgrowth in conditions like psoriasis, in small, controlled amounts, it helps close wounds and restore the skin barrier. If T. rubrum infection encourages IL-22 production, it might accidentally help nearby acne lesions heal by pushing skin cells to close the wound faster.
In the case of a pimple that has burst or been picked at, IL-22 might speed up the return of healthy skin over the spot — helping prevent secondary infection and speeding recovery.
Active Infection Can Delay Healing
It’s important to also consider the risks. While fungal immune signals might help healing in theory, having an actual fungal infection in a wound is usually bad for healing. For example, people with chronic wounds (like diabetic foot ulcers) sometimes have fungi like Candida or Trichophyton growing in them — and studies show these wounds take longer to heal.
A live fungal infection in an open acne lesion could keep the immune system busy and prevent the wound from closing. The body would keep sending immune cells to deal with the fungus, using up resources needed for healing and possibly making inflammation linger.
So timing and context matter. Using the fungus’s immune-suppressing substances — without having a real infection — might be helpful. But if T. rubrum is actually growing in the acne wound, it could make things worse.
Local vs. Whole-Body Effects
It’s also possible that T. rubrum doesn’t need to be right on the pimple to have an effect. For example, someone with a chronic fungal infection on their feet or nails might have slightly more IL-10 or more Tregs throughout their body due to the infection. These calming signals might circulate in small amounts and slightly tone down the immune system elsewhere — including the face.
This kind of general immune shift — similar to what happens with chronic worm infections — could, in theory, make acne outbreaks milder. But if it happens at all, the effect would likely be small and hard to measure.
Putting It All Together
All of this leads to an interesting idea: T. rubrum might help the skin calm down inflammation and heal faster — not by infecting acne lesions directly, but by using its immune-suppressing tricks.
Imagine a cream made from heat-killed T. rubrum or purified versions of its calming molecules (like mannan or kynurenic acid). These could be applied to acne-prone skin to gently shift the immune balance — lowering IL-17 and TNF-α while boosting IL-10. This kind of product might help reduce redness, shrink pimples, and speed up healing — all without needing live fungus.
This idea is similar to how some current skin treatments work: for example, bacterial extracts or immune-targeting drugs that reduce skin inflammation.
Of course, this idea would need careful testing. Lowering the immune response too much could let C. acnes grow unchecked or lead to other issues. But if done carefully, using fungal immune tools could become a new way to treat acne.
Conclusion
Fungi like Trichophyton rubrum are very good at hiding from the body’s immune system. They use clever tricks — like releasing calming molecules and shifting the body toward a less aggressive immune state — to stay on the skin for a long time without causing much pain or redness.
These tricks include producing special cell wall components like mannans, releasing immune-suppressing substances like kynurenic acid, and encouraging the body to create more regulatory T cells (Tregs) and anti-inflammatory cytokines like IL-10 and TGF-β. Together, these changes allow T. rubrum to cause chronic infections that are often mild and easy to overlook — like athlete’s foot or nail fungus.
Acne, on the other hand, is the opposite. It’s caused by an overly strong immune response to a usually harmless skin bacterium. The result is inflammation, pus, redness, and often scarring. In acne, the immune system is too loud — and that loudness causes damage.
By comparing these two conditions — a quiet fungal infection and a loud acne flare-up — we can ask an interesting question: can the fungus’s calming effect on the immune system help reduce the inflammation seen in acne?
Theoretically, yes.
In scientific terms, T. rubrum might reduce acne inflammation by turning down important immune signals like IL-1β, IL-17, and TNF-α, and increasing calming signals like IL-10 and TGF-β. This could lead to smaller, less painful pimples and possibly help them heal faster with fewer scars. There’s even some experimental support for this idea — studies have shown that fungal antigens from T. rubrum reduced inflammation in a serious joint infection model in rats.
But there’s an important catch.
This idea is still just a theory. No clinical studies have proven that having a fungal infection improves acne. In fact, having a live fungus on acne-prone skin could make things worse — possibly leading to fungal acne-like symptoms or interfering with the healing process. An active infection in a wound is rarely a good thing.
That’s why, if this concept is ever put into practice, it would likely use purified parts of the fungus — not the whole, live organism. These could be included in creams or gels to gently adjust the immune response in acne without causing a new infection.
In summary, the unique way T. rubrum interacts with the immune system opens up new possibilities for calming acne-related inflammation. By shifting the immune balance — reducing aggressive cytokines and boosting regulatory ones — fungal-derived treatments might someday help the skin respond more gently to C. acnes, leading to fewer breakouts and faster healing.
It’s a fascinating idea: that the same fungus behind athlete’s foot might hold the key to calming angry pimples. But for now, it remains a scientific hypothesis — one that connects two very different skin conditions through the common thread of immune regulation.
Future studies could explore fungal molecules as new acne treatments. Until then, this comparison helps us better understand how controlling inflammation — not just killing bacteria — is key to healthier skin.