ORCID Profile
0000-0003-2679-6927
Current Organisation
The University of Auckland
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Publisher: Cambridge University Press (CUP)
Date: 04-1994
DOI: 10.1017/S095026880005768X
Abstract: The general bacterial flora of 38 Tasmanian SIDS infants was examined together with faecal flora of 134 comparison infants ranging in age from birth to 6 months. The microflora of all specimens received was investigated with special emphasis on the toxigenic Escherichia coli (TEC). S les were examined for verocytotoxigenic E. coli , free faecal verocytotoxin (FVT), heat labile toxin (LT) and heat stable toxin (ST) producers with the use of a Vero cell assay and commercial kits. The findings of this study revealed a high isolation rate (39%) of TEC from SIDS infants as compared to 1.5% from the healthy comparison infants. Atypical E. coli strains were also identified during the study, including E. coli A–D. An analysis of the same specimens for rotaviral and adenoviral antigens indicated that 30% of the SIDS cases were positive as compared to 20% in the comparison group.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2MD00314G
Publisher: Wiley
Date: 03-02-2005
DOI: 10.1002/CNCR.20911
Abstract: A Phase I study of 11 pediatric patients with newly diagnosed, Stage 4 neuroblastoma was conducted using monocyte-derived dendritic cells (DC) pulsed with tumor RNA to produce antitumor vaccines (DC(RNA)). Patients received two courses of induction with carboplatin followed by standard chemotherapy, surgery, radiation, high-dose therapy, stem cell rescue, and DC(RNA) vaccine therapy. The results showed that this method for producing and administering DC(RNA) from a single leukapheresis product was both feasible and safe in this pediatric neuroblastoma population. Two courses of carboplatin maintained lymphocyte counts at normal levels. However, immune function 6 weeks after high-dose chemotherapy and stem cell rescue and prior to receiving DC(RNA) was impaired in all patients tested. There was an alteration in the ratio of CD4-positive and CD80-positive T cells. CD4-positive cell numbers were below normal, whereas CD8-positive cell numbers were above normal for all patients. In addition, CD19-positive cell numbers were below normal for all but one patient. It was found that humoral responses to recall antigens (diphtheria and tetanus) and cellular responses to mitogen and recall antigens were below normal in most patients. Despite this, two of three patients tested showed a tumor-specific humoral immune response to DC(RNA). Among the patients who had measurable disease at the time of DC(RNA) vaccine, none showed any objective tumor response. DC(RNA) vaccines were both safe and feasible in children with Stage 4 neuroblastoma. Humoral responses to tumor were detected, although remained immunosuppressed at the time of administration, limiting efficacy.
Publisher: Stichting Nase
Date: 03-2017
DOI: 10.4193/RHINO16.201
Publisher: MDPI AG
Date: 27-06-2019
Abstract: Staphylococcus aureus and Group A Streptococcus (GAS) are common occupants of the tonsils and many strains produce potent exotoxins (mitogens) that directly target T cells, which could be a driver for tonsillar hyperplasia. Tonsil tissues from 41 patients were tested for these bacteria in conjunction with profiling of B and T cells by flow cytometry. S. aureus and GAS were detected in tonsil tissue from 44% and 7%, respectively, of patients by bacteriological culture immuno-histology showed bacteria in close proximity to both B and T lymphocytes. The presence of tonsillar S. aureus did not alter B or T cell populations, whereas peripheral blood mucosal-associated invariant T (MAIT) cells were significantly increased in S. aureus culture positive in iduals (p 0.006). Alterations of tonsil CD4+ TCR Vβ family members relative to peripheral blood were evident in 29 patients. Three patients had strong TCR Vβ skewing indicative of recent exposure to superantigens, their tonsils contained mitogenic bacteria, and supernatants from these bacteria were used to partially recapitulate the skewing profile in vitro, supporting the notion that superantigens can target tonsillar T cells in situ. Tonsils are a reservoir for superantigen-producing bacteria with the capacity to alter the composition and function of key immune cells.
Publisher: Wiley
Date: 25-06-2013
DOI: 10.1038/ICB.2013.28
Abstract: Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a range of diseases, from local skin infections through to life-threatening illnesses such as toxic shock syndrome. S. aureus produces an assortment of molecules designed to evade or subvert the host immune system. One ex le is the 23 kDa staphylococcal superantigen-like protein 7 (SSL7) that simultaneously binds immunoglobulin A (IgA) and complement C5 to inhibit complement-mediated hemolytic and bactericidal activity. The avirulent bacterium Lactococcus lactis was engineered to express SSL7 so that its role in bacterial survival could be assessed without interference from other virulence factors. Expression of SSL7 by L. lactis led to significantly enhanced bacterial survival in whole human blood and prevented the membrane attack complex (C5b-9) forming on the cell wall. To further understand the mechanism of action of SSL7, the activity of wild-type SSL7 protein was compared with a panel of mutant proteins lacking the capacity to bind IgA, C5, or both IgA and C5. SSL7 potently inhibited in vitro chemotaxis of inflammatory myeloid cells in response to a pathogenic stimulus and when injected into mice, SSL7 blocked the migration of neutrophils into the peritoneum in response to an inoculum of heat-killed S. aureus. Mutagenesis of the C5-binding site on SSL7 abolished all inhibitory activity, while mutation of the IgA-binding site had only partial effects, indicating that while IgA binding enhances activity it is not essential. SSL7 is an important staphylococcal virulence factor with potent anti-inflammatory properties, which are mediated by targeting complement C5 and IgA.
Publisher: Hindawi Limited
Date: 16-09-2021
DOI: 10.1155/2021/7428955
Abstract: The purpose of this review is to summarise contemporary knowledge of sinonasal tissue remodelling during chronic rhinosinusitis (CRS), a chronic disease involving long-term inflammation of the paranasal sinuses and nasal passage. The concept of tissue remodelling has significant clinical relevance because of its potential to cause irreversibility in chronic airway tissues. Recent studies have indicated that early surgical treatment of CRS may improve clinical outcome. Tissue remodelling has been described in the literature extensively with no consensus on how remodelling is defined. This review describes various factors implicated in establishing remodelling in sinonasal tissues with a special mention of asthma as a comorbid condition. Some of the main histological features of remodelling include basement membrane thickening and collagen modulation. This may be an avenue of research with regard to targeted therapy against remodelling in CRS.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.BMC.2008.04.037
Abstract: The naturally occurring phthalide-containing antibiotics spirolaxine methyl ether, CJ-12,954, CJ-13,013, CJ-13,015, CJ-13,102, CJ-13,103, CJ-13,104 and CJ-13,108, have been reported to exhibit anti-H. pylori activity. However, the exact stereochemistry of spirolaxine methyl ether, CJ-12,954 or CJ-13,013, contributing to this observed activity has not been confirmed. The anti-H. pylori activity of several analogues of spirolaxine methyl ether, CJ-12,954 and CJ-13,013 of defined stereochemistry together with the anti-H. pylori activity of several indole analogues of the simpler phthalide-containing antibiotics CJ-13,102, CJ-13,104, CJ-13,108 and CJ-13,015 is reported herein. A 1:1 mixture of spiroacetals 5b and 6b in which the phthalide substituent exhibited (3R)-stereochemistry was sixty times more active than the corresponding 1:1 mixture of spiroacetals with (3S)-stereochemistry. Notably, the unnatural (2''S)-diastereomer of spirolaxine methyl ether exhibited more potent anti-H. pylori activity than the natural product spirolaxine methyl ether. The 4,6-dimethoxyindoles 9, 10, 11 and 13 were all found to be less active than their parent compounds 1, 2, 3 and 4, respectively. Chain-shortened 4,6-dimethoxyindole analogue 12 of CJ-13,108 3 and 4,6-dimethoxyindole-spiroacetal 13 exhibited weak anti-H. pylori activity thus providing future opportunity for drug discovery programs.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2014
DOI: 10.1007/S00430-014-0353-2
Abstract: Streptococcus pyogenes is a human pathogen which causes a spectrum of diseases ranging from pharyngitis to rheumatic fever, necrotising fasciitis and toxic shock syndrome. Development of a vaccine for S. pyogenes has been confounded both by the ersity of the disease-causing serotypes and the spectre of inadvertently stimulating autoimmunity. The S. pyogenes nuclease A (SpnA) is a recently characterised virulence factor that is highly conserved across strains and expressed during human disease. Deletion of spnA from S. pyogenes results in reduced survival of bacteria in whole human blood and attenuated virulence in a mouse model of infection. Collectively these features suggest that SpnA has potential as a vaccine candidate for S. pyogenes. Mice vaccinated subcutaneously with single or multiple doses of recombinant SpnA emulsified in Incomplete Freund's Adjuvant developed a robust and durable IgG response, including neutralising activity, to this protein. However, vaccination with rSpnA conferred no advantage in terms of lesion development, disease symptoms or colonisation levels after a sub-lethal subcutaneous challenge with S. pyogenes. Anti-SpnA serum IgG responses and neutralising activity were increased in response to challenge, indicating that SpnA is expressed in vivo. SpnA is unlikely to be a suitable antigen for a vaccine against S. pyogenes.
Publisher: Oxford University Press (OUP)
Date: 07-2004
Publisher: Elsevier BV
Date: 06-1996
DOI: 10.1016/0264-410X(95)00246-W
Abstract: Immunization with an oral vaccine composed of whole cell sonicates of Helicobacter felis plus cholera toxin (CT) can protect mice from H. felis challenge. The aim of this study was to determine whether this protective immunity was long-lived. Mice were given the vaccine then left for up to 15 months before challenge. After 15 months, all mice were still protected from H. felis infection, indicating that oral immunization using bacterial antigens plus CT can stimulate long-term local immunological memory.
Publisher: MDPI AG
Date: 21-11-2019
Abstract: Development of a vaccine to limit the impact of antibiotic resistant Neisseria gonorrhoeae is now a global priority. Serum bactericidal antibody (SBA) is a possible indicator of protective immunity to N. gonorrhoeae, but conventional assays measure colony forming units (CFU), which is time-consuming. A luminescent assay that quantifies ATP as a surrogate measure of bacterial viability was tested on N. gonorrhoeae strains FA1090, MS11 and P9-17 and compared to CFU-based readouts. There was a linear relationship between CFU and ATP levels for all three strains (r 0.9). Normal human serum (NHS) is a common source of complement for SBA assays, but needs to be screened for non-specific bactericidal activity. NHS from 10 in iduals were used for serum sensitivity assays—sensitivity values were significantly reduced with the ATP method for FA1090 (5/10, p 0.05) and MS11 (10/10, p 0.05), whereas P9-17 data were comparable for all donors. Our results suggest that measuring ATP underestimates serum sensitivity of N. gonorrhoeae and that the CFU method is a better approach. However, mouse anti-P9-17 outer membrane vesicles (OMV) SBA titres to P9-17 were comparable with both methods (r = 0.97), suggesting this assay can be used to rapidly screen sera for bactericidal antibodies to gonococci.
Publisher: Wiley
Date: 10-2002
DOI: 10.1046/J.1365-2141.2002.03717.X
Abstract: The number of dendritic cells (DC) circulating in the peripheral blood of cancer patients were monitored at multiple time points during chemotherapy and granulocyte colony-stimulating factor (G-CSF) support. DC were identified via the lack of expression of standard lineage markers and high expression of HLA-DR (LN-/DR+). The expression of DC-associated markers, including CD83, CD11c, IL-3Ralpha (CDw123) and CD86, within this LN-/DR+ population was also monitored. Maximal mobilization occurred during recovery on d 12, with a mean 32-fold increase in LN-/DR+ numbers. The most striking increase was observed in the LN-/DR+/CD83+ cell population: 12 d after commencement of treatment, the proportion of these cells had increased by approximately 120-fold when compared with baseline. Peripheral blood mononuclear cell (PBMC) and CD34+ cell numbers also peaked 12 d into the treatment regimen in most patients. These data suggest that it should be possible to acquire substantial numbers of DC from leukapheresis products collected from cancer patients undergoing a standard treatment regimen of chemotherapy and G-CSF. This strategy may be a feasible, low-risk means of acquiring cells for DC-based vaccine studies.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1096-9896(2000)9999:9999<::AID-PATH619>3.0.CO;2-H
Publisher: Frontiers Media SA
Date: 19-09-2018
Publisher: Wiley
Date: 05-10-2023
DOI: 10.1111/IMCB.12692
Publisher: Wiley
Date: 28-11-2018
DOI: 10.1002/CRE2.139
Publisher: American Society for Microbiology
Date: 31-08-2010
Abstract: Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori , we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B 6 biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B 6 biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B 6 is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori . Thus, for the first time, we identify vitamin B 6 biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens. IMPORTANCE Approximately half of the world’s population is infected with H. pylori , yet how H. pylori bacteria establish chronic infections in human hosts remains elusive. From gene array studies, we identified two genes as representing potentially novel colonization factors for H. pylori . These genes encoded enzymes involved in the synthesis of vitamin B 6 , an important molecule for many metabolic reactions in living organisms. Little is currently known regarding vitamin B 6 biosynthesis in human pathogens. We showed that mutant H. pylori bacteria lacking an enzyme involved in de novo vitamin B 6 biosynthesis, PdxA, were unable to synthesize motility appendages (flagella) and were unable to establish chronic colonization in mice. Thus, this work identifies vitamin B 6 biosynthesis enzymes as novel virulence factors for bacterial pathogens. Interestingly, a number of human pathogens, but not their mammalian hosts, possess these genes, which suggests that Pdx enzymes may represent ideal candidates for new therapeutic targets.
Publisher: Wiley
Date: 28-06-2017
DOI: 10.1002/ALR.21970
Abstract: The overproduction and stagnation of purulent mucus impair mucociliary clearance and exacerbate the symptoms of chronic rhinosinusitis (CRS). There is a clinical need for effective topical mucolytic agents to facilitate removal of mucus and improve postoperative outcomes. The effects of xylitol (5%) and dornase alfa (1 mg/mL) on mucus and mucus crusts were investigated. Viscoelasticity and viscosity of wet mucus derived from 30 CRS patients was measured with a plate rheometer. Postoperative dried mucus crust dissolution was measured by examining peripheral transparency, central transparency, and border definition of treated crust s les from 17 CRS patients. Xylitol and dornase alfa reduced wet mucus viscoelasticity at a frequency of 0.1 Hz significantly more than the saline control. Treatments also produced significantly lower viscosities than saline at a shear rate of 10 and 100 seconds Xylitol and dornase alfa may be efficacious mucolytics, encouraging the breakdown of postoperative mucus crusts and the reduction of viscoelasticity and viscosity of wet mucus. In vivo study is required to evaluate the potential of these agents in treating recalcitrant CRS.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.IJPORL.2018.07.041
Abstract: Obstructive sleep apnea (OSA) is now a more common indication for tonsillectomy than recurrent tonsillitis (RT) [1,2]. Few studies have addressed possible differences in pathogenesis between these two conditions. Children with RT and OSA are often being treated in the community with multiple courses of antibiotics before surgery. Current understanding of the role of bacteria in disorders of the tonsils is mainly based on the culture of tonsil swabs. Swab cultures reflect only a very small fraction of the bacteria present on the mucosal surface and may not represent the bacterial communities within the tonsil crypts [3,4]. This study aimed to evaluate the local lymphocyte response and associations with bacterial community composition using molecular techniques of the tonsils removed from children for RT or OSA. The palatine tonsils were removed by extracapsular dissection from 24 patients with age range one to ten years, 14 of whom had RT and 10 had OSA. The fixed tonsil tissues were evaluated for bacteria by Gram-staining and presence of connective tissue by safranin staining. B lymphocytes and T lymphocytes were also measured immunohistochemically. Finally, previously published bacterial community data for this cohort were reassessed for associations with RT and OSA, and with the observed lymphocyte patterns. In tonsils from patients with RT, large micro-colonies of bacteria were observed in the tonsil crypts, and a large number of B and T lymphocytes were noted immediately adjacent to the tonsil crypt itself. In marked contrast, the tonsils from patients with OSA had no bacteria identified, and no significant skewing of lymphocytes based on site (such as follicles or crypts). We observed that the majority of lymphocytes surrounding the bacterial micro-colonies were B lymphocytes with a mean ratio of 109:55 (B lymphocytes: T lymphocytes). Bacterial community ersity was not different between the two cohorts however, there were significant differences in bacterial community composition. Children with RT had a higher relative abundance of members from the genera Parvimonas, Prevotella, and Treponema. While children with OSA had a higher relative abundance of Haemophilus, and Capnocytophaga. These results demonstrate significant differences in the local lymphocyte response and bacterial community composition in tonsil tissue between RT and OSA patients. It suggests that the response to antibiotics used in the treatment of these two conditions may be different. Furthermore, the presence of lymphocytes in RT within the tonsil crypt outside the tonsil epithelium is a unique observation of the location of these cells.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.IJPORL.2018.07.024
Abstract: Culture-independent methods, based on bacterial 16 S rRNA gene sequencing, have been used previously to investigate the adenotonsillar microbiota. However, these studies have focused on a single s ling site (usually a surface swab). We aimed to investigate potential differences in adenotonsillar microbiota according to s ling location, both on and within the adenoids and palatine tonsils. Pediatric patients (n = 28, mean age five years) undergoing adenotonsillectomy were recruited for this study. At the time of surgery, a mucosal adenoid surface swab and an adenoid tissue biopsy was collected. Immediately following surgery, the crypts of the right and left tonsils were swabbed, and a surface and core tissue s le from the right tonsil were also collected. Bacterial 16 S rRNA gene-targeted licon sequencing was used to determine the bacterial composition of the collected s les. There was no significant difference in ersity or composition of the adenoid microbiota based on s ling site. However, the Shannon-Wiener and Inverse-Simpson ersity indices differed significantly (p < 0.05) between the microbial communities of the three different tonsil s ling sites. There was a higher average relative abundance of members from the genera Streptococcus, Actinobacillus, and Neisseria in the tonsil crypts when compared with surface and core tonsil tissue s les. Our results indicate that there is variation in bacterial ersity and composition based on s ling sites in the tonsils but not the adenoids. The difference in microbiota between the surface and the tissue may have implications for our understanding of the pathogenesis of recurrent tonsillitis and have treatment implications.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.IJPORL.2018.12.030
Abstract: Adenotonsillar and middle ear diseases result in some of the most frequently performed operations in the pediatric population worldwide. The pathogen reservoir hypothesis (PRH) suggests that the adenoids act as a reservoir of bacteria which play a potential pathogenic role in otitis media. Evidence supporting this hypothesis is limited. This study sought to comprehensively determine and compare associations between the adenotonsillar and middle ear bacterial microbiota within in idual patients via next-generation sequencing and microbial network analyses. Bacterial 16S rRNA gene-targeted licon sequencing was used to determine the bacterial composition of ten pediatric patients undergoing adenotonsillectomy and ventilation tube insertion for otitis media with effusion. At the time of surgery, swabs were taken from the adenoid surface, tonsil crypts and middle ear clefts (through the myringotomy incision). The most abundant sequences within the bacterial community at genus level across all anatomical sites were Fusobacterium, Haemophilus, Neisseria, and Porphyromonas. There was an observable difference in the relative abundance of bacterial communities, with a higher proportion of Haemophilus and Moraxella in the adenoid when compared with the middle ear. Furthermore, only one module (consisting of 4 bacterial OTUs) from one patient was identified through microbial network analyses to be significantly associated between middle ear and adenoid. In addition, microbial network analysis revealed that the adenoid and tonsil microbiota share greater similarity than do the adenoid and middle ear. The results of this study suggest that the adenoid microenvironment does not correlate to the middle ear microenvironment. A future study at the species level, and over time, is required to further investigate whether the differing relationship between the microbiota of the adenoid and middle ear rejects the pathogen reservoir hypothesis.
Publisher: Springer Science and Business Media LLC
Date: 04-05-2017
DOI: 10.1007/S00430-017-0510-5
Abstract: The TCR Vβ repertoire from patients with recurrent tonsillitis and/or tonsillar hyperplasia was examined to determine whether the TCR Vβ composition is suggestive of local superantigen activity and if so, whether it is associated with the presence of superantigen producing bacteria. Tonsil specimens were cultured aerobically to allow identification and isolation of the bacterial pathogens Staphylococcus aureus and Group A Streptococcus. TCR Vβ subset analysis of tonsil leucocytes was performed by flow cytometry. The superantigenic potential of tonsil S. aureus isolates was determined by multiplex PCR and a T-cell mitogenicity assay. Tonsils were collected from 40 patients who were predominantly pre-school-aged children undergoing surgery for either recurrent tonsillitis or tonsillar hyperplasia causing obstructive sleep apnoea. S. aureus was cultured from 23/40 and Group A Streptococcus from 5/40 patients. Both CD4
Publisher: American Society for Microbiology
Date: 08-2001
DOI: 10.1128/IAI.69.8.5186-5188.2001
Abstract: The effect of low-dose antigen exposure on the development of immunity to Helicobacter pylori infection was studied in outbred mice. Animals that were primed with a subinfectious number of H. pylori bacteria exhibited significantly lower bacterial loads after challenge with an infectious dose of pathogen (versus controls, P 0.05).
Publisher: American Society for Microbiology
Date: 02-2012
DOI: 10.1128/CVI.05446-11
Abstract: Streptococcal mitogenic exotoxin Z-2 (SMEZ-2) is a streptococcal superantigen that primarily stimulates human T cells bearing Vβ8 and mouse T cells bearing Vβ11. Mutagenesis of T cell receptor (TCR)-binding residues (W75L, K182Q, D42C) produced a mutant called M1 that was 5 -fold less active toward human peripheral blood lymphocytes and splenocytes from transgenic mice that express human CD4 and either human HLA-DR3-DQ2 or HLA-DR4-DQ8. Similarly, cytokine production in response to M1 in lymphocyte culture was rendered undetectable, and no change in the frequency of Vβ11-bearing T cells in mice receiving M1 was observed. M1 toxoid was tested as a potential vaccine conjugate. Vaccination with 1 to 10 μg M1 conjugated to ovalbumin (M1-ovalbumin) resulted in more rapid and quantitatively higher levels of anti-ovalbumin IgG, with endpoint titers being 1,000- to 10,000-fold greater than those in animals immunized with unconjugated ovalbumin. Substantially higher levels of anti-ovalbumin IgG were observed in mice transgenic for human major histocompatibility complex (MHC) class II. Substitution of M1 with an MHC class II binding mutant (DM) eliminated enhanced immunity, suggesting that M1 enhanced the delivery of antigen via MHC class II-positive antigen-presenting cells that predominate within lymphoid tissue. Immunization of animals with a conjugate consisting of M1 and ovalbumin peptide from positions 323 to 339 generated levels of anti-peptide IgG 100-fold higher than those in animals immunized with peptide alone. Coupling of a TCR-defective superantigen toxoid presents a new strategy for conjugate vaccines with the additional benefit of targeted delivery to MHC class II-bearing cells.
Publisher: Wiley
Date: 02-2001
DOI: 10.1046/J.1440-1711.2001.00975.X
Abstract: Depletion of dendritic cells from UV-B-irradiated sheep skin was investigated by monitoring migration of these cells towards regional lymph nodes. By creating and cannulating pseudoafferent lymphatic vessels draining a defined region of skin, migrating cells were collected and enumerated throughout the response to UV-B irradiation. In the present study, the effects of exposing sheep flank skin to UV-B radiation clearly demonstrated a dose-dependent increase in the migration of Langerhans cells (LC) from the UV-B-exposed area to the draining lymph node. The range of UV-B doses assessed in this study included 2.7 kJ/m2, a suberythemal dose 8 kJ/m2, 1 minimal erythemal dose (MED) 20.1 kJ/m2 40.2 kJ/m2 and 80.4 kJ/m2, 10 MED. The LC were the cells most sensitive to UV-B treatment, with exposure to 8 kJ/m2 or greater reproducibly causing a significant increase in migration. Migration of gammadelta+ dendritic cells (gammadelta+ DC) from irradiated skin was also triggered by exposure to UV-B radiation, but dose dependency was not evident within the range of UV-B doses examined. This, in conjunction with the lack of any consistent correlation between either the timing or magnitude of migration peaks of these two cell types, suggests that different mechanisms govern the egress of LC and gammadelta+ DC from the skin. It is concluded that the depression of normal immune function in the skin after exposure to erythemal doses of UV-B radiation is associated with changes in the migration patterns of epidermal dendritic cells to local lymph nodes.
Publisher: Public Library of Science (PLoS)
Date: 07-09-2017
No related grants have been discovered for Fiona Radcliff.