Pathogenesis of acne

Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.     

Toll样受体2在类固醇性痤疮中的表达

目的研究Toll样受体2（TLR2）在类固醇痤疮发病过程中的作用。方法收集62例类固醇激素性痤疮患者皮肤组织,免疫组织化学法检测TLR2的表达水平;体外培养皮肤角质形成细胞系Hacat细胞,实时定量PCR及Western blot法检测地塞米松对TLR2表达的影响。结果类固醇痤疮患者的痤疮样皮损TLR2的表达较正常组明显增高。地塞米松能显著上调静止Hacat细胞TLR2的表达;也能进一步增强痤疮丙酸杆菌刺激的Hacat细胞中TLR2的表达。结论皮质类固醇激素对TLR2表达的增强作用可能参与了类固醇激素性痤疮的发生发展。     

Susceptibility of Propionibacterium acnes and Staphylococcus epidermidis to killing by MPO-halide system products. Implication for taurine bromamine as a new candidate for topical therapy in treating acne vulgaris

INTRODUCTION: Taurine chloramine (TauCl) and taurine bromamine (TauBr) are the main haloamines produced by activated neutrophils. TauCl exerts both anti-inflammatory and microbicidal activities. Clinical studies showed that TauCl may be useful as an antimicrobial agent in the local treatment of infections. Much less is known about TauBr. Circumstantial evidence suggests that Propionibacterium acnes (PA) has a role in the inflammation of acne. Available topical therapies include antimicrobial agents which reduce total PA numbers and anti-inflammatory agents which suppress activity of the cells present in acne inflammatory lesions. In this study the bactericidal activities of TauBr and TauCl against PA and Staphylococcus epidermidis (SE), as a control strain, were investigated. Moreover, the influence of these haloamines on the generation of reactive oxygen species (ROS) by activated neutrophils was also tested. MATERIALS AND METHODS: TauBr and TauCl were prepared by reaction of taurine with HOBr and HOCl, respectively. The reaction was monitored by UV absorption spectra. The bactericidal activities of TauBr and TauCl were determined by the pourplate method. The generation of ROS by neutrophils was determined by luminol chemiluminescence assay. RESULTS: In our experimental set-up, TauBr showed stronger antibacterial activity than TauCl. Interestingly, PA was significantly more susceptible to TauBr than SE was. Moreover, TauBr at non-cytotoxic concentrations significantly reduced ROS generation by neutrophils. CONCLUSIONS: Since PA is considered to be an etiological agent in acne and ROS are closely correlated with the pathogenesis of inflammatory skin diseases, the reported data suggest that TauBr may be a good candidate for the topical therapy for acne vulgaris.     

Formation of Propionibacterium acnes biofilms on orthopaedic biomaterials and their susceptibility to antimicrobials

Failure to treat and eradicate prosthetic hip infection with systemic antibiotic regimens is usually due to the fact that the infection is associated with biofilm formation and that bacterial cells growing within a biofilm exhibit increased resistance to antimicrobial agents. In this in vitro study, we investigated the susceptibility of prosthetic hip Propionibacterium acnes and Staphylococcus spp. isolates growing within biofilms on polymethylmethacrylate (PMMA) bone cement to a range of antibiotics. All P. acnes isolates in the biofilm mode of growth demonstrated considerably greater resistance to cefamandole, ciprofloxacin and vancomycin. In contrast, only four of the eight P. acnes isolates demonstrated an increase in resistance to gentamicin. All ten Staphylococcus spp. isolates in the biofilm mode of growth exhibited large increases in resistance to gentamicin and cefamandole with eight of the ten isolates also exhibiting an increase in resistance to vancomycin. However, only three of the ten Staphylococcus spp. isolates exhibited an increase in resistance to ciprofloxacin. Biofilms were also formed on three different titanium alloys and on PMMA bone cement using P. acnes, Staphylococcus epidermidis and Staphylococcus aureus strains to determine if the underlying biomaterial surface had an effect on biofilm formation and the antimicrobial susceptibility of the bacteria growing within biofilms. Although differences in the rate at which the three strains adhered to the different biomaterials were apparent, no differences in biofilm antibiotic resistance between the biomaterials were observed. In the light of these results, it is important that the efficacy of other antibiotics against P. acnes and Staphylococcus spp. prosthetic hip isolates growing within biofilms on orthopaedic biomaterials be determined to ensure optimal treatment of orthopaedic implant infection.     

Intergeneric and intrageneric inhibition between strains of Propionibacterium acnes and micrococcaceae, particularly Staphylococcus epidermidis, isolated from normal skin and acne lesions.

Two hundred and forty-one strains or resident skin bacteria comprising 93 isolates of Propionob acterium acnes and 148 of Micrococcaceae derived from 36 acne patients and 8 control subjects were screened for their ability to inhibit 32 indicator strains, including 20 strains of P. acnes and 12 strains of Staphylococcus epidermidis derived from patients with all grades of acne and from normal skin. Fifty-three strains (22%) showed some activity against at least one indicator strain. Both broad- and narrow-spectrum inhibition was detected. Inhibitory isolates of P. acnes outnumbered inhibitory Micrococcaceae by four to one. There was a low frequency of inhibition of S. epidermidis by Micrococcaceae (2.7%) and by P. acnes (1.1%) and a higher frequency of inhibition of P. acnes by Micrococcaceae (9.5%) and by P. acnes (40.8%). Furthermore, 81.8% of the subjects sampled possessed strains inhibitory to P. acnes. The significance of this finding is, as yet, unknown. No difference in the prevalence of active strains in normal (20%) and acne (22.5%) skin was detected. These findings suggest that the possession of inhibitory strains and conversely the possession of sensitive strains does not predispose to acne.     

Complement activation in acne vulgaris: consumption of complement by comedones.

Comedones, the contents of acne lesions, were shown to consume scomplement hemolytic activity in normal serum. This consumption was stimulated by the addition of serum from patients with inflammatory acne. Absorption of acne serum with Propionibacterium acnes cells removed all stimulating activity. Immunoelectrophoretic analysis of serum incubated with comedones revealed the conversion of C3 and factor B in normal serum. The addition of acne serum resulted in cleavage of C4. In serum treated with ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, only C3 and factor B were converted. This indicates that comedones may activate complement by either the classical or the alternative pathway. It is suggested that P. acnes cells in comedonal material are responsible for the complement activation.     

Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorphonuclear leukocyte chemotaxis generated by lipase. Tetracycline hydrochloride and erythromycin base at concentrations of 10(-1) mM and 1 mM, respectively, caused 100% inhibition of PMN migration toward lipase or zymosan-activated serum. The inhibiting activity of the antibiotics was directed against cells independently of any effect on lipase. Chemotaxis by P. acnes lipase suggests a wider role for this enzyme in the inflammatory process and the pathogenesis of acne vulgaris.     

Susceptibility testing of Propionibacterium acnes comparing agar dilution with E test.

Propionibacterium acnes has been identified as a significant agent of nosocomial infections, including endophthalmitis. Data concerning susceptibility of P. acnes to newer beta-lactam antibiotics and fluoroquinolones are limited. Recent reports suggest that quinolones have activity against these organisms sufficient to warrant further study. We undertook a study to select appropriate antimicrobial agents for use in a rabbit model of P. acnes endophthalmitis. We compared the antibiotic susceptibilities of P. acnes by using the National Committee for Clinical Laboratory Standards method of agar dilution with the E test. Thirteen clinical isolates obtained from eye specimens and three American Type Culture Collection control strains were tested against 14 antibiotics. All the clinical isolates were susceptible by both methods to piperacillin, piperacillin-tazobactam, ampicillin-sulbactam, ticarcillin-clavulanate, cefotaxime, cefotetan, ceftriaxone, cefoxitin, and imipenem in addition to clindamycin but were resistant to metronidazole. The clinical P. acnes isolates also displayed high-level susceptibility to ciprofloxacin, sparfloxacin, and ofloxacin. Almost all the P. acnes strains demonstrated E-test MICs within 2 dilutions of the MICs observed by the agar dilution method. Those few strains for which discrepancies were noted exhibited E-test susceptibilities three- to fivefold dilutions lower than the agar dilution method susceptibilities but only with ampicillin-sulbactam, ticarcillin-clavulanate, and/or clindamycin. On the basis of our study, all of clinical eye isolates were susceptible to these newer antimicrobial agents and the two methods demonstrated similar susceptibility patterns.     

Susceptibility of Propionibacterium acnes to killing and degradation by human neutrophils and monocytes in vitro.

Propionibacterium acnes, the target of inflammation in acne, was tested for its sensitivity to the bactericidal and degradative functions of human polymorphonuclear leukocytes (PMN), monocytes, and their fractions. P. acnes strains were not killed by PMN under any conditions and were variably killed by monocytes in the presence of serum from acne patients. Control strains of Staphylococcus aureus and Micrococcus lysodeicticus were susceptible to both PMN and monocyte killing. P. acnes strains were also not killed by lysozyme, chymotrypsin, H2O2, human serum, PMN granule lysate, and PMN and monocyte cell lysates. The organism was sensitive to the bactericidal activity of myeloperoxidase in acid pH. In addition, P. acnes was shown to be relatively resistant to the degradative action of PMN and monocyte lysates, whereas M. lysodeicticus, S. aureus, and Staphylococcus epidermidis were all degraded to various degrees. The moieties that were liberated from P. acnes by PMN enzymes were predominantly low in molecular weight (1,000 to 25,000) and were consistent with cell wall fragments.     

Pathogenesis of acne

Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastruc-tural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.     

Complement activation in acne vulgaris: in vitro studies with Propionibacterium acnes and Propionibacterium granulosum.

To better define the role of bacteria in inflammatory acne vulgaris, we have investigated the ability of four strains of Propionibacterium acnes and three strains of Propionibacterium granulosum to activate complement. Complement activation was assayed by incubating normal human serum with varying concentrations of each strain and measuring residual total hemolytic complement activity. When serum was tested unaltered, P. acnes strains were approximately threefold more potent than an equal weight of P. granulosum in consuming complement, which could reflect classical and/or alternative pathway activation. All strains also consumed complement in serum chelated with ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, which selectively assays alternative pathway activation. Incubation of unaltered serum with both P. acnes and P. granulosum resulted in immunoelectrophoretic conversion of C4, C3, and factor B of the alternative pathway. Incubation of chelated serum resulted in conversion of C3 and factor B. These data taken together suggest that both species can activate complement through either pathway. Serum incubated with P. acnes was chemotactic for polymorphonuclear leukocytes, and this chemotactic activity was largely C5 dependent as shown by antibody inhibition. It is suggested that complement activation may occur in vivo in acne, and the inflammatory response may be contributed to by the generation of C5-dependent chemotactic factors.     

Optimization of periprosthetic culture for diagnosis of Propionibacterium acnes prosthetic joint infection

Propionibacterium acnes is increasingly recognized as an important agent of prosthetic joint infection (PJI). However, the optimum culture conditions for recovery of this organism from PJI specimens have not been determined. By applying a prolonged 28-day culture incubation to all periprosthetic specimens received for bacterial culture from 198 revision arthroplasty procedures, we retrospectively determined that a 13-day culture incubation period is necessary for the recovery of P. acnes from patients with PJI. Incubation beyond this period was associated with increasing recovery of nondiagnostic isolates: 21.7% of P. acnes isolates believed to be clinically unimportant were recovered after 13 days of incubation. Importantly, a diagnosis of P. acnes PJI would have been missed in 29.4% of patients had extended culture incubation been applied only to anaerobic culture media. Although specimens from P. acnes PJIs were more commonly associated with the presence of ≥ 2 culture media positive for growth, acute inflammation (≥ 5 neutrophils/high-power field) was observed in only 40% of patients with PJIs that had more than one specimen submitted for bacterial culture. These results support the need for a minimum culture incubation period of 13 days to be applied to both aerobic and anaerobic culture media for all periprosthetic specimens. Optimal recovery of infecting organisms from PJI specimens will be an important component in generating a universal definition for PJI due to indolent agents of infection, such as P. acnes.     

Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne.

Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that the soluble stimulating factor may be a secreted form of peptidoglycan-polysaccharide.     

Multilocus sequence typing and phylogenetic analysis of Propionibacterium acnes

Propionibacterium acnes is a commensal of human skin but is also implicated in the pathogenesis of acne vulgaris, in biofilm-associated infections of medical devices and endophthalmitis, and in infections of bone and dental root canals. Recent studies associate P. acnes with prostate cancer. As the species includes evolutionary lineages with distinct association with health and disease, there is a need for a high-resolution typing scheme. Recently, two multilocus sequence typing (MLST) schemes were reported, one based on nine and one based on seven housekeeping genes. In the present study, the two schemes were compared with reference to a phylogenetic tree based on 78 P. acnes genomes and their gene contents. Further support for a basically clonal population structure of P. acnes and a scenario of the global spread of epidemic clones of P. acnes was obtained. Compared to the Belfast scheme, the Aarhus MLST scheme (http://pacnes.mlst.net/), which is based on nine genes, offers significantly enhanced resolution and phylogenetic inferences more concordant with analyses based on a comprehensive sampling of the entire genomes, their gene contents, and their putative pathogenic potential.     

European surveillance study on the antibiotic susceptibility of Propionibacterium acnes

Propionibacterium acnes strains are recovered from infections linked to surgical procedures, foreign bodies and septicaemia. This study investigated the antibiotic susceptibility patterns of P. acnes isolates from different systemic infections and determined the genomic diversity among resistant P. acnes isolates with low-frequency restriction analysis of chromosomal DNA by pulsed-field gel electrophoresis (PFGE). In total, 304 P. acnes isolates from 13 laboratories in 13 European countries were tested against six antimicrobial agents by the NCCLS reference agar dilution method and the breakpoints recommended by the European Committee on Antimicrobial Susceptibility Testing. Blood isolates were encountered most frequently, followed by those from skin and soft tissue infections, and abdominal infections. Of the isolates examined, 2.6% were resistant to tetracycline, 15.1% to clindamycin, and 17.1% to erythromycin. No resistance was observed to linezolid, benzylpenicillin or vancomycin. There was considerable variation between countries in the proportion of resistant strains, ranging from 83% in Croatia and 60% in Italy to 0% in The Netherlands. Isolates from blood were predominant among the resistant isolates. Seventeen clones and 78 banding patterns were identified among the resistant isolates. It was concluded that antimicrobial resistance has now emerged among P. acnes isolates from systemic infections.     

Clearance of Propionibacterium acnes by kupffer cells is regulated by osteopontin through modulating the expression of p47phox

Osteopontin (OPN) is a cytokine with multiple functions, including the regulation of innate immune response. However, the detailed function and mechanism of OPN in host defense against invaded microorganisms remain unclear. In this report, we revealed that OPN could affect the clearance of Propionibacterium acnes in kupffer cells. In a murine model of P. acnes induced hepatic granuloma, OPN-deficient mice or wild-type (WT) mice treated with anti-OPN mAb exhibited more hepatic granuloma formation than WT mice. Increased infiltration of intrahepatic leukocytes, higher expression of TLRs, and significantly upregulated level of proinflammatory cytokines of liver tissue were observed in OPN-deficient mice after P. acnes challenge. Moreover, in vitro assay showed that kupffer cells isolated from OPN(-/-) mice exhibited impairment in clearance of P. acnes. Kupffer cells isolated from OPN(-/-) mice showed reduced level of NADPH oxidase-mediated reactive oxygen species (ROS) in response to P. acnes, which was regulated by NADPH oxidase subunit p47phox. Further investigation revealed that OPN interaction with αvβ3 integrin activated PI3K and ERK signal pathways, leading to the expression of p47phox. Taken together, these data demonstrated an important role of OPN in enhancing the antimicrobial innate immune response by modulation of bacterium clearance activity in kupffer cells.     

Resistance of propionibacteria to antibiotics used in the treatment of acne

Strains of propionibacteria resistant to clindamycin or clindamycin and erythromycin were isolated from four patients with acne, three of whom were receiving clindamycin. Four strains of P. acnes and one of P. granulosum with moderate levels of tetracycline resistance were isolated from 25 patients with acne being treated with tetracycline. A similar increase in tetracycline resistance was achieved by training sensitive strains in vitro. P. acnes was sensitive to sulphonamide and trimethoprim but some strains of P. granulosum were resistant to sulphonamide. Similar reports of clindamycin and erythromycin resistance from the USA suggest resistance may be increasing in isolates from patients with acne.     

Polyacrylamide gel electrophoresis (PAGE) of whole-cell proteins of cutaneous Propionibacterium species

Polyacrylamide gel electrophoresis (PAGE) was applied to the study of whole-cell proteins of cutaneous propionibacteria in an attempt to characterise possible protein patterns that may be typical for strains isolated from acne skin. Isolates were obtained from the faces of 33 individuals aged 7-16 years. Some of these subjects had apparently normal healthy skin, whereas others had acne vulgaris of varying severity. Twenty-five facial isolates of Propionibacterium acnes and eight of P. granulosum were studied. A further seven axillary strains of P. avidum were included for purely taxonomic interest. No particular protein pattern was characteristic of an isolate from acne skin; in fact the P. acnes strains from all sources appeared to be identical.     

Modulatory effect of killed Propionibacterium acnes and its purified soluble polysaccharide on peritoneal exudate cells from C57Bl/6 mice: major NKT cell recruitment and increased cytotoxicity

Propionibacterium acnes has been described as a potent adjuvant to immune responses in vitro and in vivo. Presently, we analysed the modulation of peritoneal exudate cells (PEC) by heat-killed P. acnes or its purified soluble polysaccharide (PS), both injected intraperitoneally in C57Bl/6 mice, aiming at their recruitment and cytotoxicity. Both treatments induced an increase in macrophages, immature dendritic cells, B1a lymphocytes and NK1.1(+) CD3(+) cells. The bacterium caused a remarkable increase in a NK1.1(+) CD3(+) CD4(-) CD8(-) cells subpopulation, whereas the PS component seemed responsible for the recruitment of mainly macrophage cells. To assess P. acnes and PS adjuvant effect on PEC cytotoxicity we evaluated their in vitro effect on murine B16F10 melanoma cells. The effector cells from the heat-killed bacteria and PS-treated groups lysed melanoma cells in co-cultures with PEC. Mice genetically deficient in IFN-gamma, when stimulated with P. acnes or PS, had reduced PEC cytotoxicity, and the cytotoxic effect was completely abrogated in PEC from iNOS(-/-) mice. The tumoricidal activity of PEC from P. acnes-treated mice was mediated by macrophages and NKT cells stimulated with IL-12. In PS-treated mice the cytotoxicity was mediated mainly by macrophages. Moreover, both treatments increased IL-4 and IFN-gamma production by NKT cells. In conclusion, we show that P. acnes act mainly by recruiting and activating NKT double-negative cells in PEC, which were shown to be tumoricidal in vitro when induced by IL-12. Macrophages induced by both P. acnes and PS have their antitumour effect dependent on NO production.     

Acne is not associated with yet-uncultured bacteria

Current clinical and microbiological information on acne fails to demonstrate a clear association between particular species, including Propionibacterium acnes, and disease, and the disease continues to be a considerable problem. To test if acne is associated with hitherto uncultured bacteria residing in diseased skin follicles, sequencing and phylogenetic analysis of approximately 5,700 amplified and cloned 16S rRNA genes were used to determine the microbial diversity in follicles from acne patients and healthy individuals and from the superficial skin of acne patients. Follicles from healthy skin were exclusively colonized by P. acnes, whereas the follicular microbiota of acne patients included, in addition, Staphylococcus epidermidis and minor proportions of other species. In comparison, samples from superficial skin showed a complex microbiota represented by 12 to 16 bacterial species. The findings of the study exclude the possibility that acne is associated with yet-uncultured bacteria and shows that healthy skin follicles constitute a remarkably exclusive habitat allowing colonization only by P. acnes.