Revisiting the Cutaneous Epithelium: Insights from a Nontraditional Model System Das Hautepithel Überdenken: Erkenntnisse Von Einem Einfachen Modellsystem
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414 Review Revisiting the Cutaneous Epithelium: Insights from a Nontraditional Model System Das Hautepithel überdenken: Erkenntnisse von einem einfachen Modellsystem Authors R. Augustin, T. C. G. Bosch Institution Zoological Institute, Christian-Albrechts-University Kiel Bibliography Abstract homeostasis. We highlight how work in the non- DOI http://dx.doi.org/ ! traditional model system Hydra is uncovering 10.1055/s-0042-103121 In the last 10 years, biology has made revolution- new mechanisms to old cell biological problems Online-Publikation: 21.3.2016 ary advances from century-old debates about the that provide a foundation for understanding, pre- Akt Dermatol 2016; 42: 414–420 © Georg Thieme Verlag KG relative importance of non-pathogenic bacteria. venting and in the long-term even treating skin Stuttgart · New York New applications of sequencing technologies are diseases. We demonstrate that the cutaneous ISSN 0340-2541 transforming our understanding of the biology of epithelium is an ecosystem hosting a complex the skin. Similar to all other epithelia, the skin is microbiome and that components of the innate Corresponding author Prof. Dr. Dr. h.c. colonized by an assemblage of microorganisms immune system as well as transcriptional regula- Thomas C. G. Bosch which, for the most part, peacefully coexist with tors of stem cells are involved in maintaining Zoological Institute their hosts. Alterations to microbial communities homeostasis between epithelia and their resident Christian-Albrechts-University are associated with, and likely contribute to, a microbiota. We conclude that beneficial bacterial- Olshausenstraße 40 number of cutaneous disorders. This review focu- host interactions should be considered an integral 24098 Kiel ses on the host factors that shape and maintain part of skin biology and that nontraditional [email protected] skin microbial communities, and the reciprocal model systems can provide a holistic understand- role of microbes in pathogen defense and tissue ing of the cutaneous epithelium. “Nothing in biology makes sense except in the light with bacteria, archaea, viruses, fungi, and numer- of evolution.” [1] ous other microbial and eukaryotic species (●" Fig.1a) [2,3, 4]. These resident microbes influ- ence fitness and thus ecologically important traits Introduction: The cutaneous epithelium of their hosts [5,6]. is an ecosystem and host to complex Since 150 years bacteriologists, microbiologists microbial communities and immunologists have focused on bacteria as ! pathogens. This approach has led to enormous in- Our understanding of the biology of the skin is in sights in the battle between the invading harmful the midst of a major transition. Extraordinary re- microbes and the host and also opened up the This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. cent progress in molecular genetics in a number opportunity to develop efficient strategies to fight of model systems, novel sequencing technologies infections. Today we know that most bacteria are and comparative bioinformatics is revealing de- not harmful but beneficial and are playing a key tails about the cutaneous epithelium that under- ecological role. In an updated literature survey, mine prior conceptions, and highlight the value only about 200 of the millions of bacteria that of an evolutionary perspective. The naïve concep- interact with humans are regarded as emerging tion that the skin is an entity, with some ectoder- or reemerging pathogens [7,8]. Inexpensive, high mal and mesodermal cell types interacting with throughput sequencing has uncovered a new each other, is fading as the complex and dynamic world of relationships between skin cells and nature of organisms as metaorganisms is be- their colonizing microbes [9,10, 11,12]. Using coming better understood. All animals, ranging mass spectrometry and DNA sequencing, the from simple invertebrates to humans, are host to bacteria and chemical compounds found on hu- complex microbial communities and, therefore, man skin have been sampled and mapped across must be considered a meta-organism, i.e. the the body in a series of 3-D images [13]. The chem- macroscopic host in synergistic interdependence ical signature (secretome) found on the skin is Augustin R, Bosch TCG. Revisiting the Cutaneous Epithelium:… Akt Dermatol 2016; 42: 414–420 Review 415 Fig. 1 a Multicellular organisms are metaorgan- isms comprising the macroscopic host and its synergistic interdependence with bacteria, archaea, fungi, and numerous other microbial and eukary- otic species including algal symbiont (modified from [4]). b Hydra, a basal animal with a simple gross anatomy (tentacles, head and foot) and a simple epithelio-muscular bilayer, has emerged 550 million years ago. The fresh water cnidarian is a close relative to corals and jellyfish with their enormous impact on environment on earth. In recent years this non-traditional model has shown to be useful answering fundamental questions in biology, concerning development, immunity and host-microbe interactions (modified from [39]). thought to be unique to an individual and is distinct for certain infections. The results highlight an association between the skin’s body parts. It harbors specific combinations of bacteria and a microbial inhabitants and resolution of infection. But do the distinct mix of molecules from foods eaten and even medicines bacteria that normally colonize our skin directly help to clear the taken. This newfound awareness of the skin as an ecosystem pathogenic bacteria? Or is the microbiome only another indicator, colonized by a diverse milieu of microorganisms presents addi- but not the cause of bacterial infection? While we have to wait for tional layers of complexity for dermatologists and raises many answers to these questions, the Haemophilus study provides a questions that are being addressed by new and interdisciplinary convincing example of how the ecology of human skin can influ- research programs. The field of ecological evolutionary develop- ence health and disease. Microbes therefore matter! Intriguingly, mental biology (Eco-Evo-Devo) attempts to study and model this one of the abundant bacterial taxa among the infection-resolvers new view of nature by organizing concepts such as develop- was Propionibacterium acnes, a microbe associated with skin acne. mental symbiosis and developmental plasticity into evolutionary Thus it seems that under some circumstances bacterial species or theory [14]. “Biology has entered a new era with the capacity to strains such as Propionibacterium acnes may cause skin disease understand that an organism’s genetics and fitness are inclusive of and under other conditions may guard the skin and keep it its microbiome” [15]. For dermatologists this means that they healthy. Principles of ecology appear to determine the homeosta- must approach their field with an entirely new concept of nature. sis between skin-dwelling bacteria and their host tissue. Recent studies highlight that in addition to chancroid, the pathological outcome of many human and animal diseases is influenced by Bacteria matter: recent lessons from Haemophilus the co-existence with the residing microbial communities. Dis- ! turbed host-microbial interactions and related inflammatory Symbiotic microorganisms occupy a wide range of skin niches [9, signaling play an important role in the etiology of a number of 10, 11,12] and may even protect against invasion by more harmful chronic inflammatory disorders affecting barrier organs (e.g. or pathogenic organisms. Recent evidence supporting this view inflammatory bowel diseases, psoriasis), but also in metabolic comes from a study focused on Haemophilus ducreyi [16]. This diseases and certain forms of cancer [17,18,19, 20, 21]. bacterium causes chancroid, a relatively common form of sexually transmitted genital ulcers that is endemic in certain parts of Africa and Asia and facilitates the transmission of HIV-1. The bacterium How Hydra, a non-traditional epithelial model system, has also been implicated in nonsexually transmitted cutaneous can help us to understand the complexity of cutaneous This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. ulcers in children in the tropics. Interestingly, infected individuals defense can either clear the infection or develop pustules that eventually ! form abscesses. What is the reason behind these differences? Defining the individual microbe-host conversations in a given Taking advantage of a unique human skin infection model, metaorganism (●" Fig. 1a) is a challenging but necessary step on researchers at Indiana University have found evidence to suggest the path to understanding the function of the associations as a that the makeup of the skins microbiome plays a major role in whole. Untangling the complex interactions requires simple whether an individual can clear the H. ducreyi bacterial infection animal models with only a few specific bacterial species. Such without intervention [16]. The investigators compared the skin models can function as living test tubes and may be key to dis- microbiome in patients who resolved their H. ducreyi infection to secting the fundamental principles that underlie all host-micro- those who did not. Strikingly, preinfection skin microbiomes of be interactions. Here we introduce Hydra (●" Fig.1b; ●" Fig. 2a pustule formers and resolvers have distinct community structures and ●" Fig. 2b) as such a non-traditional