Microbial Symbiosis with the Innate Immune Defense System of the Skin
01 Oct 2011-Journal of Investigative Dermatology (NIH Public Access)-Vol. 131, Iss: 10, pp 1974-1980
TL;DR: Observations indicate that the normal human skin microflora protects skin via various modes of action, a conclusion supported by many lines of evidence associating diseases such as acne, atopic dermatitis, psoriasis and rosacea with an imbalance of the microFLora even in the absence of classical infection.
About: This article is published in Journal of Investigative Dermatology.The article was published on 2011-10-01 and is currently open access. It has received 300 citations till now. The article focuses on the topics: Innate immune system & Human skin.
Citations
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TL;DR: In this paper, the skin microbiota has an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function, and skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor.
Abstract: Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.
839 citations
TL;DR: Reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus, showing how commensal skin bacteria protect against pathogens and how dysbiosis of the skin microbiome can lead to disease.
Abstract: The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
683 citations
Cites background from "Microbial Symbiosis with the Innate..."
...aureus, other bacterial species found on normal skin appear to aid in normal immune homeostasis (21)....
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01 Jan 2012
TL;DR: In mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function and this findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.
634 citations
TL;DR: An updated view on how teleost skin, gills and gut immune cells and molecules, function in response to pathogens and commensals is provided and some of the future avenues that the field of fish mucosal immunity may follow in the next years are highlighted.
527 citations
TL;DR: Results show the microbiota extends within the dermis, therefore enabling physical contact between bacteria and various cells below the basement membrane, and show that normal commensal bacterial communities directly communicate with the host in a tissue previously thought to be sterile.
Abstract: Commensal microbes on the skin surface influence the behavior of cells below the epidermis. We hypothesized that bacteria or their products exist below the surface epithelium and thus permit physical interaction between microbes and dermal cells. Here, to test this hypothesis, we employed multiple independent detection techniques for bacteria including qPCR, Gram-staining, immunofluorescence, and in situ hybridization. Bacteria were consistently detectable within the dermis and dermal adipose of normal human skin. Sequencing of DNA from dermis and dermal adipose tissue identified bacterial 16S rRNA reflective of a diverse and partially distinct microbial community in each skin compartment. These results show the microbiota extends within the dermis, therefore enabling physical contact between bacteria and various cells below the basement membrane. These observations show that normal commensal bacterial communities directly communicate with the host in a tissue previously thought to be sterile.
353 citations
References
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TL;DR: As the need for new antibiotics becomes more pressing, could the design of anti-infective drugs based on the design principles these molecules teach us?
Abstract: Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?
7,657 citations
"Microbial Symbiosis with the Innate..." refers background in this paper
...These molecules are produced in all organs by a variety of cell types and are major contributors to immune defense (Nizet et al., 2001; Zasloff, 2002)....
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TL;DR: It is shown that SCFA–GPR43 interactions profoundly affect inflammatory responses, and GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
Abstract: The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases. One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in 'healthy' microbiota such as Bifidobacterium and Bacteriodes, and a concurrent reduction in SCFAs. Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis. SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43(-/-) immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
2,515 citations
"Microbial Symbiosis with the Innate..." refers background in this paper
...…which are produced by fermentation of dietary fiber by intestinal microbiota, suppressed inflammation by reducing activity and recruitment of neutrophils through binding to G-protein-coupled receptor 43 (GPR 43, also known as free fatty acid receptor 2) on the cell surface (Maslowski et al., 2009)....
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TL;DR: This topographical and temporal survey of body sites from 10 healthy human individuals sampled over time provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.
Abstract: Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.
2,252 citations
"Microbial Symbiosis with the Innate..." refers background in this paper
...Grice et al. have characterized the topographical and temporal diversity of microbiome in the healthy human skin of a small population of individuals with a 16S rRNA gene phylotyping (Grice et al., 2009)....
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TL;DR: It is reported here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus and that molecules of the bacterial microbiota can mediate the critical balance between health and disease.
Abstract: Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
2,097 citations
"Microbial Symbiosis with the Innate..." refers background in this paper
...…demonstrated that Polysaccharide A produced by Bacteroides fragilis suppressed pro-inflammatory interleukin (IL)-17 production by intestinal immune cells exposed to pathogenic bacteria, Helicobacter pylori, through a functional requirement for IL-10-producing CD4+ T cells (Mazmanian et al., 2008)....
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TL;DR: A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus.
Abstract: Background The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and β-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human β-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis. Methods The expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested...
1,807 citations
"Microbial Symbiosis with the Innate..." refers background in this paper
...…of cathelicidin and hBDs following acute wounding Increased expression of RNase7 and psoriasin Frequent bacterial infections S. aureus colonization (Ong et al., 2002) (Miller et al., 2005) (Hata et al., 2010) (Mallbris et al., 2010) (Harder et al., 2010) (Maintz and Novak, 2011) Psoriasis Abnormal…...
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...A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript inflammation (Hata et al., 2010; Lande et al., 2007; Ong et al., 2002)....
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...…of TLR5 Infrequency of Propionibacterium and Actinobacteria species Predominance of Firmicutes species Infrequent bacterial infection (Ong et al., 2002) (Bensch et al., 1995) (Miller et al., 2005) (Harder and Schroder, 2005) Rosacea Abnormal expression of cathelicidin Abnormal…...
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