Evaluation of the role of humoral immunity through assessment of monocyte-FC gamma receptors in pathogenesis of acne vulgaris (original) (raw)
Related papers
Classic diseases revisited: Acne: a review of immunologic and microbiologic factors
Postgraduate Medical Journal, 1999
Acne vulgaris is a self-limiting skin disorder seen primarily in adolescents, whose aetiology appears to be multifactorial. The four main aetiological factors are hypercornification of the pilosebaceous duct, increased sebum production, colonization with Propionibacterium acnes, and subsequently the production of inflammation. Considerable investigation has addressed the immunologic reaction to extracellular products produced by the acne-causing organism, P acnes. The immunologic response involves both humoral and cellmediated pathways. Further research should clarify the role of complement, cytotoxins, and neutrophils in this acne-forming response.
British Journal of Dermatology, 2007
Background Propionibacterium acnes has been strongly implicated in inflammatory acne. However, its role in the disease is unclear. It has been hypothesized that an immune response to P. acnes and/or P. acnes heat shock proteins (HSPs) may play a role in the pathogenesis of inflammatory acne. Objectives To compare the cell-mediated immune response to P. acnes and HSPs in acne patients, nonacne controls and individuals with resolved acne. Methods The proliferative response of peripheral blood mononuclear cells (PBMC) from acne patients, resolved acne donors and healthy controls to P. acnes, P. acnes HSP60 and HSP70, and mycobacterial HSPs was assessed by lymphocyte transformation assay (LTA). The proliferative response of purified CD4+ T cells was further analysed by limiting dilution analysis (LDA). Contingency tables (G-test) were used to analyse the proportion of individuals in each group showing a positive proliferative response for LTA or data fitting single-hit kinetics for LDA. Results Analysis of stimulation of PBMC with P. acnes, P. acnes HSP60 and HSP70 in the LTA showed the proportion of positive responders to be independent of subject group. However, the proportion of acne patients with a positive response to mycobacterial HSPs was significantly higher than those for the other subject groups. Analysis of LDA data showed the proportion of resolved donors with responses to P. acnes fitting the single-hit kinetics model to be significantly lower than those of the other groups. There were no significant differences in responses to other antigens. Conclusions The significantly lower proportion of resolved donors demonstrating a single-hit kinetics response to P. acnes by LDA may represent negative regulation of the CD4+ T-cell response to P. acnes in these subjects.
New developments in our understanding of acne pathogenesis and treatment
Experimental Dermatology, 2009
Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005-2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may
Current Concepts in Acne Pathogenesis: Pathways to Inflammation
Seminars in cutaneous medicine and surgery, 2018
Acne is a disease of pilosebaceous inflammation. Pivotal in pathogenesis are the roles of hormones (insulin, insulin-like growth factor-1, androgens), Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile. Innate immune responses are induced through interaction with toll-like receptors and inflammasome activation initially and subsequently through adaptive immune activation. These insights into pathogenic inflammatory pathways can translate into novel therapeutic approaches for acne. Semin Cutan Med Surg 37(supp3):S60-S62 ©2018 published by Frontline Medical Communication.
The Role of Innate Immunity in the Pathogenesis of Acne
Dermatology, 2003
Acne is a multifactorial disease of the pilosebaceous follicle. The most significant pathogenetic factors of acne are: abnormal ductal keratinization, increased sebum secretion, abnormalities of the microbial flora and inflammation. The pilosebaceous unit is an immunocompetent organ. Keratinocytes and sebocytes may act as immune cells capable of pathogen recognition and abnormal lipid presentation, and they might have an important role in initiating and perpetuating the activation of both innate and adaptive immune responses. The elements of the skin immune system are involved in the development of both noninflammatory and inflammatory acne lesions.
British Journal of Dermatology, 2004
Background Keratinocytes form the first line of defence in the skin and alert the host to danger by the production of a number of cytokines and chemokines. However, the interaction of commensal microorganisms with keratinocytes has not been well studied. Objectives To investigate the effect of viable and nonviable cells of Propionibacterium acnes in both exponential and stationary growth phases, and of P. acnes GroEL on cytokine production by human primary keratinocytes. Methods Actively proliferating or contact-inhibited keratinocytes were cocultured with viable or formaldehyde-killed P. acnes cells in either the exponential or stationary phase of growth. Culture supernatants were assayed by enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-1a, tumour necrosis factor (TNF)-a and granulocyte ⁄ macrophage colony-stimulating factor (GM-CSF). Keratinocytes were also stimulated with different concentrations of P. acnes GroEL and supernatants assayed for cytokines. Results Viable P. acnes in the stationary phase of growth stimulated keratinocyte monolayers to produce significantly higher amounts of IL-1a, TNF-a and GM-CSF than unstimulated keratinocytes. Viable exponential-phase bacteria stimulated production of significantly higher amounts of TNF-a and GM-CSF but these levels were significantly lower than those for stimulation with stationary-phase bacteria. Nonviable P. acnes from either growth phase was not able to stimulate cytokine production. P. acnes GroEL at concentrations in the range 0AE05-1AE0 lg mL)1 was able to induce increased production of cytokines by keratinocytes in a dose-dependent manner. This was analogous to stimulation with Escherichia coli GroEL. Conclusions Stimulation of cytokine production by P. acnes and P. acnes GroEL may be important in the pathogenesis of inflammatory acne vulgaris and may have wider implications for the immunomodulation of the human immune system by commensal skin microorganisms.
G2A Attenuates Propionibacterium acnes Induction of Inflammatory Cytokines in Human Monocytes
Annals of dermatology, 2017
Acne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium. To elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA. Our studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers. G2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne ther...
What is the pathogenesis of acne?
Experimental Dermatology, 2005
For a long time, the mantra of acne pathogenesis debates has been that acne vulgaris lesions develop when (supposedly largely androgen-mediated) increased sebum production, ductal hypercornification, and propionibacteria come together with local inflammatory process in the unlucky affected individual. And yet, the exact sequence, precise interdependence, and choreography of pathogenic events in acne, especially the 'match that lights the fire' have remained surprisingly unclear, despite the venerable tradition of acne research over the past century. However, exciting recent progress in this-conceptually long somewhat stagnant, yet clinically, psychologically, and socioeconomically highly relevant-everyday battlefield of skin pathology encourages one to critically revisit conventional concepts of acne pathogenesis. Also, this provides a good opportunity for defining more sharply key open questions and intriguing acne characteritics whose underlying biological basis has far too long remained uninvestigated, and to emphasize promising new acne research avenues off-the-beaten-track-in the hope of promoting the corresponding development of innovative strategies for acne management.
Folia Histochemica et Cytobiologica, 2009
Propionibacterium acnes (P. acnes) has been implicated in the pathogenesis of acne vulgaris which is the most common cutaneous disorder. It has a proinflammatory activity and takes part in immune reactions modulating the Th1/Th2 cellular response. The exposure of dendritic cells (DCs) to whole bacteria, their components, cytokines or other inflammatory stimuli and infectious agents induces differentiation from immature DCs into antigen-presenting mature DCs. The aim of the study was to evaluate the capability of P. acnes to induce the maturation of DCs. We stimulated monocyte derived dendritic cells (Mo-DCs) from acne patients with various concetrations of heat-killed P. acnes (10 6-10 8 bacteria/ml) cultured from acne lesions. The results showed an increase in CD80+/CD86+/DR+ and CD83+/CD1a+/DR+ cells percentage depending on the concetration of P. acnes. The expression of CD83 and CD80 (shown as the mean fluorescence intensity-MFI) increased with higher concetrations of P. acnes. There were also significant correlations between MFI of CD83, CD80, CD86 and concetration of P. acnes. The study showed that P. acnes in the concetration of 10 8 bacteria/ml is most effective in the induction of Mo-DCs maturation. Futher studies concerning the influence on the function of T cells are needed.