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In published literature this difference is taken as a given, without many studies carefully dissecting why it should be so.

  • Dermatophytes, i.e., skin-infecting fungi, are keratinophile (keratin-loving) and keratinolytic (capable of breaking down keratin) because they use keratin as a nutrient (1).
  • A plausible hypothesis is that anthropophilic dermatophytes inhibit or evade local immune responses in order to be able to live on human skin and associated keratinized tissues such as hair and nails.
  • Since zoophilic dermatophyte-human encounters are accidental, such dermatophytes wouldn’t have developed strategies to evade/inhibit human immune responses. As such, they’re more likely to inadvertently provoke strong acute immune responses that eliminate them, i.e., why zoophilic dermatophytoses are acute but also self-healing.
  • Hypothesis because there isn’t conclusive proof yet.
  • Two ways to explore differences between anthropophilic and zoophilic fungi that cause dermatophytosis are to compare the types of immune responses they induce and to compare their genomes and proteomes.
    • In a few in vitro studies, human keratinocytes (KC) were infected with anthropophilic and zoophilic dermatophytes (2, 3).
    • KC infected with the former secreted only a few cytokines (eotaxin-2, IL-8, -16) while when infected with the latter, they secreted a much broader range of cytokines (IL-1beta, -2, -4, -5, -6, -8, -10, -13, -15, -16, IFN-gamma, TGF-beta).
  • Why such a difference in immune responses elicited by anthropophilic and zoophilic dermatophytes?
    • One possibility is that the cell walls of anthropophilic dermatophytes is immunosuppressive. This was shown for Trichophyton rubrum cell wall sugars (mannans) (3, 4, 5, 6).
    • Response to local inflammation is predictable. Usually macrophages stream in from blood circulation. Their task is to swarm the site, engulf the source of inflammation, usually a microbe that has penetrated the barrier and seeks to set up shop, and wall it off and/or eliminate it.
    • In the case of anthropophilic  T. rubrum, such sugars (mannans) inhibited mouse macrophages from phagocytosing (engulfing) the fungal conidia and could even induce their death (7). T. rubrum is the dominant cause of dermatophysis, responsible for >90% of cases (8, 9).
  • Immune status of those infected also plays a role in difference in infection outcomes. Since anthropophilic dermatophytes are ubiquitous in human environments, why doesn’t everyone suffer from chronic dermatophyte infections?
    • Chronic dermatophytosis susceptibility is associated with atopy, allergy (10), and poverty, i.e., poor nutritional status. In other words, individuals with tendency for dysregulated immune responses are more likely to develop chronic dermatophytosis.
    • Having evolved to live on human keratin, anthropophilic, and not zoophilic, dermatophytes would be under active selection pressure to exploit deficiencies and deviations in human immune responses that help them establish chronic residence, an easier task in those with dysregulated immune function.
  • Study of dermatophytes and the diseases they can cause in some humans currently suffers from several drawbacks.
    • One, lack of appropriate models. Both guinea pigs and mice are used for experimental infections but problem is they develop disease only in response to zoophilic, and not anthropophilic dermatophytes (11). In vitro studies of human cell-dermatophyte co-cultures are more useful but they aren’t being used imaginatively.
    • Two, few studies compare anthropophilic and zoophilic dermatophytes, let alone compare response of human keratinocytes, macrophages and T cells to them in the same study.
    • Three, lack of genetic tools, which improved only in the last few years with the sequencing of seven dermatophyte species by the Broad Institute in Boston, MA, USA (12).
    • Four, since dermatophytes aren’t considered serious pathogens, funding opportunities are limited and few scientists specialize in studying them (13).

Bibliography

  1. Vermout, Sandy, et al. “Pathogenesis of dermatophytosis.” Mycopathologia 166.5-6 (2008): 267-275.
  2. Shiraki, Yumi, et al. “Cytokine secretion profiles of human keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae infections.” Journal of medical microbiology 55.9 (2006): 1175-1185. Page on microbiologyresearch.org
  3. Tani, Kenji, et al. “The effect of dermatophytes on cytokine production by human keratinocytes.” Archives of dermatological research 299.8 (2007): 381-387.
  4. Blake, John S., et al. “An immunoinhibitory cell wall glycoprotein (mannan) from Trichophyton rubrum.” Journal of investigative dermatology 96.5 (1991): 657-661. Page on nature.com
  5. Dahl, Mark V. “Suppression of immunity and inflammation by products produced by dermatophytes.” Journal of the American Academy of Dermatology 28.5 (1993): S19-S23
  6. García-Madrid, Luz, et al. “Trichophyton rubrum manipulates the innate immune functions of human keratinocytes.” Open Life Sciences 6.6 (2011): 902-910. Page on degruyter.com
  7. Campos, M. R. M., et al. “Stimulation, inhibition and death of macrophages infected with Trichophyton rubrum.” Microbes and infection 8.2 (2006): 372-379).
  8. Aly, Raza. “Ecology and epidemiology of dermatophyte infections.” Journal of the American Academy of Dermatology 31.3 (1994): S21-S25.
  9. Havlickova, Blanka, Viktor A. Czaika, and Markus Friedrich. “Epidemiological trends in skin mycoses worldwide.” Mycoses 51.s4 (2008): 2-15. Page on dermatologiapediatrica.net
  10. Woodfolk, Judith A. “Allergy and dermatophytes.” Clinical microbiology reviews 18.1 (2005): 30-43. Page on nih.gov
  11. Achterman, Rebecca Rashid, and Theodore C. White. “Dermatophyte virulence factors: identifying and analyzing genes that may contribute to chronic or acute skin infections.” International journal of microbiology 2012 (2011). Page on hindawi.com
  12. Dermatophyte Comparative Database
  13. Achterman, Rebecca Rashid, and Theodore C. White. “A foot in the door for dermatophyte research.” PLoS Pathog 8.3 (2012): e1002564. Page on plospathogens.org

https://www.quora.com/Why-does-zoophilic-dermatophitis-cause-acute-infection-unlike-anthropophilic-ones-which-cause-chronic-infection/answer/Tirumalai-Kamala

 

 

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