Neutrophil Recruitment to Noninvasive MRSA at the Stratum Corneum of Human Skin Mediates Transient Colonization

Schulz, Anja; Jiang, Long; Vor, Lisanne de; Ehrström, Marcus; Wermeling, Fredrik; Eidsmo, Liv; Melican, Keira

doi:10.1016/j.celrep.2019.09.055

Cited by 25 publications

(21 citation statements)

References 48 publications

(52 reference statements)

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“…Several separate reports demonstrate that immunodeficient mice support the engraftment of human skin 26 , 27 . Adult human skin-derived from either medical wastes (elective plastic surgery) 28 , 29 or tissue culture-derived engineered skin (keratinocytes and fibroblasts) 24 engrafts successfully in immunodeficient mice. Allogeneic adult human-peripheral blood mononuclear cells (PBMCs) have been introduced into these models to mimic human immune cell-skin interactions with infectious agents 24 , 29 .…”

Section: Introductionmentioning

confidence: 99%

“…Adult human skin-derived from either medical wastes (elective plastic surgery) 28 , 29 or tissue culture-derived engineered skin (keratinocytes and fibroblasts) 24 engrafts successfully in immunodeficient mice. Allogeneic adult human-peripheral blood mononuclear cells (PBMCs) have been introduced into these models to mimic human immune cell-skin interactions with infectious agents 24 , 29 . Although these mouse models demonstrate successful engraftment and development of transplanted human skin and are amenable to the transplantation of allogeneic PBMCs, said platforms are not currently coupled with the engraftment of autologous lymphoid tissues that are critical for a de novo immune response.…”

Section: Introductionmentioning

confidence: 99%

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Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

Agarwal

Beatty

et al. 2020

Sci Rep

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The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the skin are generated by introducing human skin grafts to immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized rodent models developed with human lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of human skin, autologous lymphoid tissues, and autologous immune cells in a rodent model has not yet been achieved, though it could provide a means of studying the human immune response to infection in the human skin. Here, we introduce the human Skin and Immune System (hSIS)-humanized NOD- scid IL2Rγ null (NSG) mouse and Sprague–Dawley-Rag2 tm2hera Il2rγ tm1hera (SRG) rat models, co-engrafted with human full-thickness fetal skin, autologous fetal lymphoid tissues, and autologous fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents demonstrate the development of human full-thickness skin, along with autologous lymphoid tissues, and autologous immune cells. These models also support human skin infection following intradermal inoculation with community-associated methicillin-resistant Staphylococcus aureus . The co-engraftment of these human skin and immune system components into a single humanized rodent model could provide a platform for studying human skin infections.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

Agarwal

Beatty

et al. 2020

Sci Rep

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“…By measuring significantly upregulated human IL8 expression in skin biopsies, they were able to show the reaction of the human skin towards S. aureus. Moreover, they demonstrated that human IL8 is able to recruit murine neutrophils, which contribute to controlling MRSA growth on the human skin [ 208 ]. In another study, van Dalen et al investigated the interaction of human langerin with S. aureus WTA.…”

Section: Implications Of Staphylococcal Host Adaptation For Murinementioning

confidence: 99%

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Mrochen

Oliveira

Raafat

et al. 2020

IJMS

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Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future.

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“…For example, Soong et al (2015) demonstrated that toxin-deficient, agr-mutants of S. aureus are able to persist on the human skin by stimulating autophagy. In addition, epicutaneously swabbed S. aureus on human skin xenografts led to local production of IL-8, which induced neutrophil migration to the skin to promote bacterial clearance (Schulz et al, 2019). Studies involving human skin xenograft infections are not widely used and thus represent an exciting opportunity in the dermatology field to translate the immunologic findings from mouse skin infection models to human skin.…”

Section: Human Skin Xenograft Modelmentioning

confidence: 99%

Research Techniques Made Simple: Mouse Bacterial Skin Infection Models for Immunity Research

Youn

Archer

Miller

2020

Journal of Investigative Dermatology

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Bacterial skin infections are a major societal health burden and are increasingly difficult to treat owing to the emergence of antibiotic-resistant strains such as community-acquired methicillin-resistant Staphylococcus aureus. Understanding the immunologic mechanisms that provide durable protection against skin infections has the potential to guide the development of immunotherapies and vaccines to engage the host immune response to combat these antibiotic-resistant strains. To this end, mouse skin infection models allow researchers to examine host immunity by investigating the timing, inoculum, route of infection and the causative bacterial species in different wild-type mouse backgrounds as well as in knockout, transgenic, and other types of genetically engineered mouse strains. To recapitulate the various types of human skin infections, many different mouse models have been developed. For example, four models frequently used in dermatological research are based on the route of infection, including (i) subcutaneous infection models, (ii) intradermal infection models, (iii) wound infection models, and (iv) epicutaneous infection models. In this article, we will describe these skin infection models in detail along with their advantages and limitations. In addition, we will discuss how humanized mouse models such as the human skin xenograft on immunocompromised mice might be used in bacterial skin infection research.

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Neutrophil Recruitment to Noninvasive MRSA at the Stratum Corneum of Human Skin Mediates Transient Colonization

Cited by 25 publications

References 48 publications

Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Research Techniques Made Simple: Mouse Bacterial Skin Infection Models for Immunity Research

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