S. aureus TF3378 on AD skin can skew T cell responses via LC toward imbalanced Th1/Th2 skin immunity.
Background: Staphylococcus aureus (S. aureus) is frequently detected in the skin of patients with atopic dermatitis (AD), and involved in the flare of AD. There are some evidence-specific strains of S. aureus affect the severity of AD. However, the mechanism of predominant colonization and the aggravation of dermatitis by certain strains of S. aureus in the patients with AD are still unknown.Objective: To reveal the characteristics of S. aureus from patients with AD (S. aureus-AD), we analyzed the interaction of S. aureus-AD and keratinocytes in comparison with those of S. aureus laboratory strains (S. aureus-stand.). Methods:We stimulated HaCaT cells, keratinocyte cell line, and human epidermal keratinocytes by heat-killed S. aureus strains, then evaluated immune response of keratinocytes by ELISA, immunofluorescence staining, and flow cytometry.Results: Upon incubation with keratinocytes, three out of four strains of heat-killed S. aureus-AD were strongly agglutinated inside the cytoplasm. In the cells, they are located in lysosomes and promoted the secretion of interleukin-1α (IL-1α). These reactions were not observed by any of four strains of S. aureus-stand. and S. epidermidis and were abolished by the treatment of S. aureus with proteinase K. Moreover, the IL-1α secretion was diminished by the inhibition of Toll-like receptor 9 (TLR9). Conclusion: S. aureus-AD accumulates in lysosome of keratinocytes by means of bacterial cell wall proteins and induces IL-1α via TLR9. K E Y W O R D S atopic dermatitis, dermatology, innate immunity, microbiome, staphylococcus aureus 1 | INTRODUCTION Atopic dermatitis (AD) is a common chronic skin disease characterized by pruritus and recurrent eczematous lesions. 1 There is a strong correlation between filaggrin (FLG) mutations and AD, but not all carriers of FLG mutation develop AD, 2 suggesting the involvement of other causative or aggravating factors in the pathogenesis of AD. Many patients with AD frequently suffer from cutaneous infections by Staphylococcus aureus (S. aureus). Moreover, S. aureus is commonly isolated from patients with AD, even from apparently non-lesion skin. 3 Furthermore, S. aureus colonization has been shown to be associated with AD severity and observed even before the onset of AD in infants. 4 A previous study of the skin microbiome of patients with AD revealed reduced diversity and high Staphylococcus proportions in flares of untreated AD, 5 whereas Staphylococcus epidermidis (S. epidermidis) predominates on the skin surface of healthy individuals. In murine models, S. aureus colonization and low diversity of the microbiome drive AD-like lesions in the skin. 6Compared to standard S. aureus strains, S. aureus isolated from AD skin are able to induce different innate immune responses. S. aureus from AD skin are internalized into keratinocytes and accumulate in lysosomes with inducing IL-1α secretion via TLR9. Specific surface proteins of S. aureus from AD skin are responsible for their internalization.
Pityriasis lichenoides et varioliformis acuta (PLEVA) is a cutaneous inflammatory disease of unknown etiology. It has been suggested that infection can be a trigger of PLEVA. Here, we report a case of PLEVA associated with a mixed vaccine injection.A 13-month-old girl was referred to our dermatology department with a 21-day history of multiple erythematous papules without itch. She had received her first vaccine injection against the measles-rubella (MR) and fourth vaccine injection against the haemophilus influenzae b (Hib) and pneumococcus, 7 days before the onset of the eruption. She had a history of persistent cloaca, but otherwise did not have any symptoms. Eruptions appeared on her abdomen and gradually spread over her entire body. When she visited our hospital, erythematous scaly papules and papulonecrotic lesions developed on her trunk, proximal limbs, and forehead. The rash was most prominent on her chest and abdomen ( Figure 1A,B F I G U R E 1 A, Erythematous scaly papules and papulonecrotic lesions on the front of the patient's trunk. B, The same eruptions were seen on her back. C, The biopsy specimen showed marked hyperkeratosis and parakeratosis of the stratum corneum, acanthosis, and intercellular edema in the epidermis. In the dermis, lymphohistiocytic infiltration and erythrocytes extravasation were observed around capillaries (Hematoxylin & Eosin (H&E), 920). D, Numerous apoptotic keratinocytes, exocytosis, and focal interface change were noted (H&E, 960)This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Background Optineurin (OPTN) is associated with several human diseases, including amyotrophic lateral sclerosis (ALS), and is involved in various cellular processes, including autophagy. Optineurin regulates the expression of interferon beta (IFNβ), which plays a central role in the innate immune response to viral infection. However, the role of optineurin in response to viral infection has not been fully clarified. It is known that optineurin-deficient cells produce more IFNβ than wild-type cells following viral infection. In this study, we investigate the reasons for, and effects of, IFNβ overproduction during optineurin deficiency both in vitro and in vivo. Methods To investigate the mechanism of IFNβ overproduction, viral nucleic acids in infected cells were quantified by RT-qPCR and the autophagic activity of optineurin-deficient cells was determined to understand the basis for the intracellular accumulation of viral nucleic acids. Moreover, viral infection experiments using optineurin-disrupted (Optn-KO) animals were performed with several viruses. Results IFNβ overproduction following viral infection was observed not only in several types of optineurin-deficient cell lines but also in Optn-KO mice and human ALS patient cells carrying mutations in OPTN. IFNβ overproduction in Optn-KO cells was revealed to be caused by excessive accumulation of viral nucleic acids, which was a consequence of reduced autophagic activity caused by the loss of optineurin. Additionally, IFNβ overproduction in Optn-KO mice suppressed viral proliferation, resulting in increased mouse survival following viral challenge. Conclusion Our findings indicate that the combination of optineurin deficiency and viral infection leads to IFNβ overproduction in vitro and in vivo. The effects of optineurin deficiency are elicited by viral infection, therefore, viral infection may be implicated in the development of optineurin-related diseases.
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