Innate and Adaptive Immunity in Orolabial Herpes Simplex

Oral mucosa is a frequent site of primary herpes simplex virus type 1 (HSV-1) infection, whereas intraoral recurrent disease is very rare. Instead, reactivation from latency predominantly results in asymptomatic HSV shedding to saliva or recurrent labial herpes (RLH) with highly individual frequency. The current study aimed to elucidate the role of human oral innate and acquired immune mechanisms in modulation of HSV infection in orolabial region. Saliva was found to neutralize HSV-1, and to protect cells from infection independently of salivary antibodies. Neutralization capacity was higher in saliva from asymptomatic HSV-seropositive individuals compared to subjects with history of RLH or seronegative controls. Neutralization was at least partially associated with salivary lactoferrin content. Further, lactoferrin and peroxidase-generated hypothiocyanite were found to either neutralize HSV-1 or interfere with HSV-1 replication, whereas lysozyme displayed no anti-HSV-1 activity. Lactoferrin was also shown to modulate HSV-1 infection by inhibiting keratinocyte proliferation. RLH susceptibility was further found to be associated with Th2 biased cytokine responses against HSV, and a higher level of anti- HSV-IgG with Th2 polarization, indicating lack of efficiency of humoral response in the control of HSV disease. In a three-dimensional cell culture, keratinocytes were found to support both lytic and nonproductive infection, suggesting HSV persistence in epithelial cells, and further emphasizing the importance of peripheral immune control of HSV. These results suggest that certain innate salivary antimicrobial compounds and Th1 type cellular responses are critically important in protecting the host against HSV disease, implying possible applications in drug, vaccine and gene therapy design.Synnynnäinen ja hankittu immuniteetti suun alueen herpes Simplex virus –infektiossa Herpes simplex tyyppi 1 virus (HSV-1) aiheuttaa tavallisimmin suun alueen infektioita. Ensi-infektio saadaan yleensä suun limakalvon kautta, mutta reaktivaatiota seuraava infektio ilmenee vain harvoin suun sisällä. Tavallisimmin reaktivaatiosta on seurauksena joko viruksen oireeton eritys sylkeen tai huuliherpes, joiden ilmenemisessä on suuria yksilöllisiä vaihteluita. Tässä työssä on tutkittu synnynnäisen ja hankitun immuniteetin vaikutusta HSV:n suun alueen ilmentymiin. Syljen havaittiin sekä neutraloivan HSV:ta, että suojaavan soluja infektiolta. Nämä tapahtumat olivat riippumattomia syljen vasta-aineista. Syljen HSV:ta neutraloiva vaikutus oli suurempi oireettomilla HSV-seropositiivisilla henkilöillä kuin henkilöillä, joilla ajoittain ilmenee huuliherpestä sekä seronegatiivisilla kontrolleilla. Neutralisaation tehokkuus oli ainakin osittain riippuvainen syljen laktoferriinipitoisuudesta. Syljen laktoferriini ja peroksidaasisysteemin tuottama hypotiosyanaatti lisäksi joko neutraloivat HSV:ta tai estivät sen lisääntymistä kohdesoluissa. Lysotsyymillä ei ollut vaikutusta infektion kulkuun. Laktoferriini vaikutti HSV-infektioon lisäksi hidastamalla keratinosyyttien jakautumista. Huuliherpestaipumukseen liittyi taipumus tuottaa Th2- tyypin sytokiinejä sekä korkea määrä Th2-tyypin HSV-IgG-vasta-aineita. Kerrostuneessa epiteelimallissa tehdyssä tutkimuksessa HSV aiheutti sekä lyyttisen että nonproduktiivisen infektion. Tämä viittaa HSV:n mahdolliseen kykyyn aiheuttaa persistoiva infektio myös keratinosyyteissä, jolloin perifeerinen HSV:n immuunikontrolli olisi vielä luultuakin tärkeämpi osa HSV-reaktivaation hallintaa. Yhteenvetona voidaan todeta, että syljen synnynnäiset puolustustekijät sekä Th1- tyypin immuunivaste suojelevat oireiselta perifeeriseltä HSV-infektiolta. Näitä tuloksia voidaan hyödyntää HSV:n lääkehoito-, rokote- ja geeniterapiasovelluksissa.Siirretty Doriast

Human lactoferrin but not lysozyme neutralizes HSV-1 and inhibits HSV-1 replication and cell-to-cell spread

The frequent oral shedding of herpes simplex virus type 1 (HSV-1) in the absence of clinical disease suggests that symptomatic HSV-1 recurrences may be inhibited by the mucosal environment. Indeed, saliva has been shown to contain substances with anti-HSV activity. In the current study, we investigated the anti-HSV-1 activity of human lactoferrin (hLf) and lysozyme (hLz), two highly cationic polypeptides of the mucosal innate defence system

Acute rhinosinusitis - are we forgetting the possibility of a dental origin? A retrospective study of 385 patients

Background: Odontogenic sinusitis (OS) is a common but underdiagnosed form of acute rhinosinusitis (ARS). OS carries no specific characteristics, but unilateral symptoms and certain microbiological as well as radiological findings indicate odontogenic origin. Aims/objectives: We studied the proportion of OS in ARS patients, the presence and associations of unilateral symptoms, and possible OS microbial and radiological findings. In addition, we investigated how this condition is recognised among ear, nose and throat specialists and radiologists. Materials and methods: All 676 ARS patients treated in the Department of Otorhinolaryngology at Helsinki University Hospital in 2013 were retrospectively enrolled. The data were collected from patients' hospital medical records, the laboratory database and radiological reports. Results: Odontogenic origin of ARS was suspected in 59 (15.3%) patients. Altogether (29.9%) 115 patients complained of unilateral symptoms and these were found to associate with probable oral microbial findings (p <.001). These findings covered 20.2% of isolates. Teeth were mentioned in 89.6% of the radiological reports.Peer reviewe

Smoking or poor oral hygiene do not predispose to peritonsillar abscesses via changes in oral flora

Aim: The purpose of this prospective study was to determine if there is a difference in number and distribution of salivary bacteria between patients with tonsillar infection and healthy volunteers. Background: The etiology of peritonsillar abscess (PTA) is unclear. Smoking, periodontal disease, and infection of minor salivary glands have been suggested as predisposing factors for PTA. Material and methods: Patients with acute tonsillitis (AT) (n = 54), peritonsillitis (PT) (n = 36), PTA (n = 58), and healthy volunteers (n = 52) were prospectively recruited and evaluated. Saliva bacteria were analyzed with flow cytometry. Patients and their treating physicians completed a questionnaire about patients' current disease, smoking habits, alcohol consumption, and oral health. Results: There were no differences in the total number of saliva bacteria between patients with acute throat infection and healthy volunteers (p = .104) or between AT, PT, and PTA patients (p = .273). Smoking habits, alcohol consumption, oral hygiene, or prior antibiotics had no effect on total amount of salivary bacteria in patients with acute throat infection. Conclusions: The effects of smoking on salivary bacteria do not seem to be the mechanism that promotes development of PTA in smokers.Peer reviewe

Odontogenic causes complicating the chronic rhinosinusitis diagnosis

Objectives Chronic rhinosinusitis (CRS) frequently stems from a dental origin, although odontogenic sinusitis (OS) remains underdiagnosed amongst different professionals. This study aimed to explore how often odontogenic causes are considered when diagnosing CRS. Materials and methods Patient records from 374 new CRS patients treated at a tertiary-level ear, nose, and throat (ENT) clinic were selected. Entries and radiological reports were assessed exploring how often dentition was mentioned and OS was suspected, how often radiologists reported maxillary teeth, and how commonly typical OS microbial findings and unilateral symptoms occurred. Results Although 10.1% of the CRS diagnoses were connected to possible dental issues, teeth were not mentioned for 73.8% of patients. Radiological reports were available from 267 computed or cone beam computed tomographies, of which 25.1% did not mention the maxillary teeth. The reported maxillary teeth pathology was not considered in 31/64 (48.4%) cases. Unilateral symptoms associated with apical periodontitis (OR = 2.49, 95% CI 1.27-4.89, p = 0.008). Microbial samples were available from 88 patients, for whom Staphylococcus aureus was the most common finding (17% of samples). Conclusions Odontogenic causes are often overlooked when diagnosing CRS. To provide adequate treatment, routine assessment of patient's dental history and status, careful radiograph evaluation, and utilization of microbial findings should be performed. Close cooperation with dentists is mandatory.Peer reviewe

Peritonsillar abscess may not always be a complication of acute tonsillitis: A prospective cohort study

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (pPeer reviewe

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake

Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43nM in static settings and 2.4M in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested -lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.Peer reviewe

The relationship between oral diseases and infectious complications in patients under dialysis

Objectives Association was investigated between oral health before dialysis and the incidence of systemic infections during dialysis. We hypothesized that low-grade systemic inflammation caused by poor oral health associates with infectious episodes in patients on dialysis, despite earlier eradication of oral infection foci. Subjects and methods A total of 117 patients (46 with peritoneal and 71 with hemodialysis) were examined and treated at predialysis stage and followed up during dialysis. Number of infection episodes and microorganisms cultured from blood and peritoneal fluid were analyzed. Number of teeth, periodontal inflammatory burden, and total dental index scores were assessed, and salivary matrix metalloproteinase 8, triggering receptor on myeloid cells 1, peptidoglycan recognition protein 1 (PGLYRP1), and interleukin-1 beta were measured. Results In hemodialysis, 134 infection episodes were recorded, while peritoneal dialysis group had 77 peritonitis episodes. Culture-negative samples were 69% in hemodialysis and 23% in peritoneal dialysis group. Staphylococci were the most frequently associated microorganisms. Infections during dialysis did neither associate with oral health parameters nor associate with salivary inflammatory biomarkers, except for PGLYRP1, which associated with number of infection episodes during hemodialysis (p = .046). Conclusions A number of infection episodes during hemodialysis were associated with salivary PGLYRP1 but not the other salivary markers or oral infection markers.Peer reviewe

Triage and urgent dental care for COVID-19 patients in the Hospital District of Helsinki and Uusimaa

Objective This paper describes and reports the patient-specific characteristics of an urgent dental care clinic for COVID-19 infected, suspected, exposed or quarantined patients from March to December 2020 in the Hospital District of Helsinki and Uusimaa, Finland. Material and methods The triage and the treatment protocol were established based on the scientific data. Patient files were evaluated from the hospital district's electronic medical record system. IBM SPSS software was used for statistical analysis. Results There were 1114 consultations and 257 visits at the clinic. Most of the patients were generally healthy with mean age of 35, had toothache and were suspected to be SARS-CoV-2 positive. Seventeen of the patients received positive tests for COVID-19 infection. The main treatment was tooth extraction, mostly due to caries. Statistically significant differences between COVID-19 infected and other patients occurred in age (45 vs 34 years-of-age, p = .009) and number of teeth (25 vs 28, p = .031). No SARS-CoV-2 infection transmission chains were traced to the clinic. Conclusion During the challenging pandemic time, patients were carefully screened by specialists in clinical dentistry and treated safely and effectively. Patient-specific characteristics revealed no differences between COVID-19 infected and other patients in terms of symptoms or treatment needs.Peer reviewe