Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania.

Some Ts in nuclear DNA of trypanosomes and Leishmania are hydroxylated and glucosylated to yield base J (ß-D-glucosyl-hydroxymethyluracil). In Leishmania, about 99% of J is located in telomeric repeats. We show here that most of the remaining J is located at chromosome-internal RNA polymerase II termination sites. This internal J and telomeric J can be reduced by a knockout of J-binding protein 2 (JBP2), an enzyme involved in the first step of J biosynthesis. J levels are further reduced by growing Leishmania JBP2 knockout cells in BrdU-containing medium, resulting in cell death. The loss of internal J in JBP2 knockout cells is accompanied by massive readthrough at RNA polymerase II termination sites. The readthrough varies between transcription units but may extend over 100 kb. We conclude that J is required for proper transcription termination and infer that the absence of internal J kills Leishmania by massive readthrough of transcriptional stops.

Unintentional injury deaths associated with sport and recreation in Québec, Canada, 2006-2019.

OBJECTIVES: This study examined trends in the frequencies and rates of deaths associated with unintentional injuries in sport and recreation in Québec, Canada, for the period January 2006-December 2019. METHODS: In this descriptive retrospective study, data were extracted from the database of the Bureau du coroner du Québec. Incidence rates were calculated using participation data from the Étude des blessures subies au cours de la pratique d'activités récréatives et sportives au Québec (ÉBARS) and Canadian census population data. Poisson regression was used to investigate changes in death rates over the 14-year period by estimating incidence rate ratios. RESULTS: There were 1937 unintentional injury deaths and the population-based death rate was 1.72 per 100 000 person-years. The participation-based rate was 1.40 per 100 000 participant-years, considering the 24 matching activities in both ÉBARS' editions. Using both population-based and participation-based denominators, separate analyses consistently showed declining death rates in non-motorised navigation and cycling. Deaths related to all-terrain vehicles, snowmobiles, swimming, cycling, motorised navigation and non-motorised navigation activities accounted for 80.2% of all deaths. Drowning was documented as a cause of death in 39.3% of all fatalities. Males represented 86.8% of all deaths, with males aged 18-24 years and 65 and over having the highest rates. CONCLUSION: The death rates of unintentional injury deaths associated with non-motorised navigation and cycling declined, from January 2006 to December 2019. The characteristics and mechanisms of drowning deaths and fatalities that occurred in activities associated with higher death frequencies and rates need to be further investigated.

Comparing the Drop Vertical Jump Tracking Performance of the Azure Kinect to the Kinect V2.

Traditional motion analysis systems are impractical for widespread screening of non-contact anterior cruciate ligament (ACL) injury risk. The Kinect V2 has been identified as a portable and reliable alternative but was replaced by the Azure Kinect. We hypothesize that the Azure Kinect will assess drop vertical jump (DVJ) parameters associated with ACL injury risk with similar accuracy to its predecessor, the Kinect V2. Sixty-nine participants performed DVJs while being recorded by both the Azure Kinect and the Kinect V2 simultaneously. Our software analyzed the data to identify initial coronal, peak coronal, and peak sagittal knee angles. Agreement between the two systems was evaluated using the intraclass correlation coefficient (ICC). There was poor agreement between the Azure Kinect and the Kinect V2 for initial and peak coronal angles (ICC values ranging from 0.135 to 0.446), and moderate agreement for peak sagittal angles (ICC = 0.608, 0.655 for left and right knees, respectively). At this point in time, the Azure Kinect system is not a reliable successor to the Kinect V2 system for assessment of initial coronal, peak coronal, and peak sagittal angles during a DVJ, despite demonstrating superior tracking of continuous knee angles. Alternative motion analysis systems should be explored.

Should my recommendation letter be written by artificial intelligence?

SummaryLetters of recommendation are increasingly important for the residency match. We assessed whether an artificial intelligence (AI) tool could help in writing letters of recommendation by analyzing recommendation letters written by 3 academic staff and AI duplicate versions for 13 applicants. The preferred letters were selected by 3 blinded orthopedic program directors based on a pre-determined set of criteria. The first orthopedic program director selected the AI letter for 31% of applicants, and the 2 remaining program directors selected the AI letter for 38% of applicants, with the staff-written versions selected more often by all of the program directors (p < 0.05). The first program director recognized only 15% of the AI-written letters, the second was able to identify 92%, and the third director identified 77% of AI-written letters (p < 0.05).

Total hip arthroplasty with monobloc press-fit acetabular components and large-diameter bearings for atypical acetabula is safe: a consecutive case series of 125 hips with mean follow-up of 9 years.

BACKGROUND: Large-diameter head (LDH) total hip arthroplasty (THA) with a monobloc acetabular component improves hip stability. However, obtaining initial press-fit stability is quite challenging in atypical acetabula. The purpose of this study was to assess primary and secondary fixation of monobloc cups in atypical acetabula. METHODS: In this consecutive case series, the local arthroplasty database was used to retrospectively identify patients with secondary osteoarthritis who underwent primary hip replacement with press-fit only LDH monobloc acetabular components between 2005 and 2018 and who had a minimum of 2 years of follow-up. Radiographic evaluation was performed at last follow-up, and patient-reported outcome measures (PROMs) were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Forgotten Joint Score (FJS), and the Patient's Joint Perception (PJP) question. RESULTS: One hundred and six LDH THAs and 19 hip resurfacings were included in the study. Preoperative diagnoses included hip dysplasia (36.8%), Legg-Calve-Perthes disease (32.0%), osteoarthritis with acetabular deficiency (17.6%), periacetabular osteotomy (8.0%), arthrodesis (4.0%), and osteopetrosis (1.6%). After a mean follow-up of 9.2 years, no aseptic loosening of the acetabular component was recorded nor observed on radiologic review. There were 13 (10.4%) revisions unrelated to the acetabular component fixation. The mean WOMAC and FJS scores were 9.2 and 80.9, respectively. In response to the PJP question, 49.4% of the patients perceived their hip as natural, 19.1% as an artificial joint with no restriction, 31.5% as an artificial joint with restriction, and none as a non-functional joint. CONCLUSION: Primary press-fit fixation of monobloc acetabular components with LDH implanted in atypical acetabula led to secondary fixation in all cases with low revision and complication rates and great functional outcomes. With careful surgical technique and experience, systematic use of supplemental screw fixation is not essential in THA with atypical acetabula.

Crystalline silica exposure in patients with rheumatoid arthritis and systemic sclerosis: a nationwide cross-sectional survey.

OBJECTIVES: Develop and validate a thorough exposure questionnaire to comprehensively explore crystalline silica (SiO2) exposure in the general population (gender-specific, occupational and non-occupational) and in patients with autoimmune diseases (rheumatoid arthritis (RA), systemic sclerosis (SSc)). METHODS: Lifetime exposures to SiO2 in occupational and non-occupational settings were assessed using a thorough exposure questionnaire. The questionnaire was applied to a general population panel (n = 2911) sampled from the French rolling census, and to unselected patients with SSc (n = 100) and RA (n = 97). Global (GES), occupational (OES) and non-occupational (NOES) exposure scores were assessed in SSc and RA patients, and compared with up to four controls from the general population, matched by age group, sex and tobacco consumption. RESULTS: Patients had higher GES than their matched controls (SSc: P = 0.001; RA: P < 0.0001) due to higher OES (P < 0.0001 for SSc and RA). Men had higher GES than women (SSc: P < 0.0001; RA: P = 0.002) due to higher OES (P < 0.0001 for SSc and RA). The NOES did not differ between men and women. In SSc patients: Men had higher GES than controls (P < 0.0001). Men and women with SSc had higher OES than controls (P < 0.0001). In RA patients: GES and OES were higher in both men (P = 0.00521; P < 0.0001) and women (P < 0.0001; P < 0.0001) than in their respective controls. Women had higher NOES than controls (P = 0.045). CONCLUSION: The lifetime SiO2 exposure gap between RA and SSc patients and controls was substantially due to occupational exposure. In both diseases, men had higher exposure scores than women.

Exposure to inorganic particles in paediatric sarcoidosis: the PEDIASARC study.

Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.

Genome-Wide Patterns of Bracovirus Chromosomal Integration into Multiple Host Tissues during Parasitism.

Bracoviruses are domesticated viruses found in parasitic wasp genomes. They are composed of genes of nudiviral origin that are involved in particle production and proviral segments containing virulence genes that are necessary for parasitism success. During particle production, proviral segments are amplified and individually packaged as DNA circles in nucleocapsids. These particles are injected by parasitic wasps into host larvae together with their eggs. Bracovirus circles of two wasp species were reported to undergo chromosomal integration in parasitized host hemocytes, through a conserved sequence named the host integration motif (HIM). Here, we used bulk Illumina sequencing to survey integrations of Cotesia typhae bracovirus circles in the DNA of its host, the maize corn borer (Sesamia nonagrioides), 7 days after parasitism. First, assembly and annotation of a high-quality genome for C. typhae enabled us to characterize 27 proviral segments clustered in proviral loci. Using these data, we characterized large numbers of chromosomal integrations (from 12 to 85 events per host haploid genome) for all 16 bracovirus circles containing a HIM. Integrations were found in four S. nonagrioides tissues and in the body of a caterpillar in which parasitism had failed. The 12 remaining circles do not integrate but are maintained at high levels in host tissues. Surprisingly, we found that HIM-mediated chromosomal integration in the wasp germ line has occurred accidentally at least six times during evolution. Overall, our study furthers our understanding of wasp-host genome interactions and supports HIM-mediated chromosomal integration as a possible mechanism of horizontal transfer from wasps to their hosts. IMPORTANCE Bracoviruses are endogenous domesticated viruses of parasitoid wasps that are injected together with wasp eggs into wasp host larvae during parasitism. Several studies have shown that some DNA circles packaged into bracovirus particles become integrated into host somatic genomes during parasitism, but the phenomenon has never been studied using nontargeted approaches. Here, we use bulk Illumina sequencing to systematically characterize and quantify bracovirus circle integrations that occur in four tissues of the Mediterranean corn borer (Sesamia nonagrioides) during parasitism by the Cotesia typhae wasp. Our analysis reveals that all circles containing a HIM integrate at substantial levels (from 12 to 85 integrations per host cell, in total) in all tissues, while other circles do not integrate. In addition to shedding new light on wasp-bracovirus-host interactions, our study supports HIM-mediated chromosomal integration of bracovirus as a possible source of wasp-to-host horizontal transfer, with long-term evolutionary consequences.

Current global perspectives on silicosis-Convergence of old and newly emergent hazards.

Silicosis not a disease of the past. It is an irreversible, fibrotic lung disease specifically caused by exposure to respirable crystalline silica (RCS) dust. Over 20,000 incident cases of silicosis were identified in 2017 and millions of workers continue to be exposed to RCS. Identified case numbers are however a substantial underestimation due to deficiencies in reporting systems and occupational respiratory health surveillance programmes in many countries. Insecure workers, immigrants and workers in small businesses are at particular risk of more intense RCS exposure. Much of the focus of research and prevention activities has been on the mining sector. Hazardous RCS exposure however occurs in a wide range of occupational setting which receive less attention, in particular the construction industry. Recent outbreaks of silicosis associated with the fabrication of domestic kitchen benchtops from high-silica content artificial stone have been particularly notable because of the young age of affected workers, short duration of RCS exposure and often rapid disease progression. Developments in nanotechnology and hydraulic fracking provide further examples of how rapid changes in technology and industrial processes require governments to maintain constant vigilance to identify and control potential sources of RCS exposure. Despite countries around the world dealing with similar issues related to RCS exposure, there is an absence of sustained global public health response including lack of consensus of an occupational exposure limit that would provide protection to workers. Although there are complex challenges, global elimination of silicosis must remain the goal.

Estimating the Force of Infection for Dengue Virus Using Repeated Serosurveys, Ouagadougou, Burkina Faso.

Because of limited data on dengue virus in Burkina Faso, we conducted 4 consecutive age-stratified longitudinal serologic surveys, ≈6 months apart, among persons 1-55 years of age, during June 2015-March 2017, which included a 2016 outbreak. The seroconversion rate before the serosurvey enrollment was estimated by binomial regression, taking age as the duration of exposure, and assuming constant force of infection (FOI) over age and calendar time. We calculated FOI between consecutive surveys and rate ratios for potentially associated characteristics based on seroconversion using the duration of intervals. Among 2,897 persons at enrollment, 66.3% were IgG-positive, and estimated annual FOI was 5.95%. Of 1,269 enrollees participating in all 4 serosurveys, 438 were IgG-negative at enrollment. The annualized FOI ranged from 10% to 20% (during the 2016 outbreak). Overall, we observed high FOI for dengue. These results could support decision-making about control and preventive measures for dengue.

WHO guidance on ethics in outbreaks and the COVID-19 pandemic: a critical appraisal.

In 2016, following pandemic influenza threats and the 2014-2016 Ebola virus disease outbreaks, the WHO developed a guidance document for managing ethical issues in infectious disease outbreaks. In this article, we analyse some ethical issues that have had a predominant role in decision making in response to the current COVID-19 pandemic but were absent or not addressed in the same ways in the 2016 guidance document. A pandemic results in a health crisis and social and political crises both nationally and globally. The ethical implications of these global effects should be properly identified so that appropriate actions can be taken globally and not just in national isolation. Our analysis, which is a starting point to test the broader relevance of the 2016 WHO document that remains the only available guidance document applicable globally, concludes that the WHO guidance should be updated to provide reasoned and thoughtful comprehensive ethics advice for the sound management of the current and future pandemics.

Collaborative research and knowledge translation on road crashes in Burkina Faso: the police perspective 18 months on.

In this commentary, we present a follow-up of two articles published in 2017 and 2018 about road traffic crashes, which is an important public health issue in Africa and Burkina Faso. The first article reported on a research project, conducted in partnership with local actors involved in road safety, carried out in Ouagadougou in 2015. Its aim was to test the effectiveness, acceptability, and capacity of a surveillance system to assess the number of road traffic crashes and their consequences on the health of crash victims. Several knowledge translation activities were carried out to maximize its impact and were reported in the 2018 article published in HRPS: monthly reports presenting the research data, large-format printed maps distributed to the city's police stations, and a deliberative workshop held at the end of the research project. The present commentary presents our efforts to deepen our understanding of the impacts of the knowledge translation strategy, based on follow-up interviews, 18 months after the workshop, with the heads of the road traffic crash units in Ouagadougou police stations (n = 5). Several benefits were reported by respondents. Their involvement in the process prompted them to broaden their knowledge of other ways of dealing with the issue of road crashes. This led them, sometimes with their colleagues, to intervene differently: more rapid response at collision sites, increased surveillance of dangerous intersections, user awareness-raising on the importance of the highway code, etc. However, sustaining these actions over the longer term has proven difficult. Several lessons were derived from this experience, regarding the importance of producing useful and locally applicable research data, of ensuring the acceptability of the technologies used for data collection, of using collaborative approaches in research and knowledge translation, of ensuring the visibility of actions undertaken by actors in the field, and of involving decision-makers in the research process to maximize its impacts.

Trauma in northern Quebec, 2005-2014: epidemiologic features, transfers and patient outcomes.

BACKGROUND: The Inuit people residing in Nunavik, Quebec, are vulnerable to major trauma owing to environmental and social factors; however, there is no systematic data collection for trauma in Nunavik, and, apart from data regarding patients who are transferred to tertiary care centres, no data enter the Quebec trauma registry directly from Nunavik. We performed a study to characterize the epidemiologic features of trauma in Nunavik, and describe indications for transfer and outcomes of patients referred to the tertiary trauma centre. METHODS: We collected data retrospectively for all patients with trauma admitted to the Centre de santé Tulattavik de l'Ungava in Kuujjuaq from 2005 to 2014. Sociodemographic, injury and health services data were extracted. The data were analyzed in conjunction with coroners' reports on death from trauma in Nunavik. RESULTS: A total of 797 trauma cases were identified. The most common causes of injury were motor vehicle collisions (258 cases [32.4%]), falls (137 [17.2%]) and blunt assault (95 [11.9%]). One-third of patients (262 [32.9%]) were transferred to the tertiary care centre in Montréal. The incidence rate of major trauma (Injury Severity Score > 12) was 18.1 and 21.7 per 10 000 person-years in the Kuujjuaq region and the Puvirnituq region, respectively, which translates to a relative risk (RR) of 4 compared to the Quebec population. The disparity observed in trauma mortality rate was even greater, with an RR of 47.6 compared to the Quebec population. CONCLUSION: The study showed major disparity in trauma incidence and mortality rate between Nunavik and the province of Quebec. Our findings allow for a better understanding of the burden of injury and regional trauma mortality in Nunavik, and recommendations for optimization of the trauma system in this unique setting.

Quantitative trait loci involved in the reproductive success of a parasitoid wasp.

Dissecting the genetic basis of intraspecific variations in life history traits is essential to understand their evolution, notably for potential biocontrol agents. Such variations are observed in the endoparasitoid Cotesia typhae (Hymenoptera: Braconidae), specialized on the pest Sesamia nonagrioides (Lepidoptera: Noctuidae). Previously, we identified two strains of C. typhae that differed significantly for life history traits on an allopatric host population. To investigate the genetic basis underlying these phenotypic differences, we used a quantitative trait locus (QTL) approach based on restriction site-associated DNA markers. The characteristic of C. typhae reproduction allowed us generating sisters sharing almost the same genetic content, named clonal sibship. Crosses between individuals from the two strains were performed to generate F2 and F8 recombinant CSS. The genotypes of 181 clonal sibships were determined as well as the phenotypes of the corresponding 4,000 females. Informative markers were then used to build a high-quality genetic map. These 465 markers spanned a total length of 1,300 cM and were organized in 10 linkage groups which corresponded to the number of C. typhae chromosomes. Three QTLs were detected for parasitism success and two for offspring number, while none were identified for sex ratio. The QTLs explained, respectively, 27.7% and 24.5% of the phenotypic variation observed. The gene content of the genomic intervals was investigated based on the genome of C. congregata and revealed 67 interesting candidates, as potentially involved in the studied traits, including components of the venom and of the symbiotic virus (bracovirus) shown to be necessary for parasitism success in related wasps.

Paediatric sarcoidosis.

Paediatric sarcoidosis is an extremely rare disease characterized by a granulomatous inflammation. The estimated incidence is 0.6-1.02/100,000 children, but in the absence of international registers, the disease is probably under-reported. Its pathophysiologic basis is not clearly understood but the current hypothesis is a combination of a genetic predisposition and an environmental exposure that could be either organic or mineral. Contrary to adult forms of the disease, general symptoms are often at the forefront at diagnosis. In its most frequent form, paediatric sarcoidosis is a multi-organ disorder affecting preferentially the lungs, the lymphatic system and the liver, but all organs can be affected. This review aims to provide an overview of current knowledge on sarcoidosis in children, providing a summary of the data available from cohort studies on the presentation, the management and the evolution of the disease in this specific population.

Evaluation of Effectiveness of a Community-Based Intervention for Control of Dengue Virus Vector, Ouagadougou, Burkina Faso.

We evaluated the effectiveness of a community-based intervention for dengue vector control in Ouagadougou, the capital city of Burkina Faso. Households in the intervention (n = 287) and control (n = 289) neighborhoods were randomly sampled and the outcomes collected before the intervention (October 2015) and after the intervention (October 2016). The intervention reduced residents' exposure to dengue vector bites (vector saliva biomarker difference -0.08 [95% CI -0.11 to -0.04]). The pupae index declined in the intervention neighborhood (from 162.14 to 99.03) and increased in the control neighborhood (from 218.72 to 255.67). Residents in the intervention neighborhood were less likely to associate dengue with malaria (risk ratio 0.70 [95% CI 0.58-0.84]) and had increased knowledge about dengue symptoms (risk ratio 1.44 [95% CI 1.22-1.69]). Our study showed that well-planned, evidence/community-based interventions that control exposure to dengue vectors are feasible and effective in urban settings in Africa that have limited resources.

How Older Adults Experience an Emergency Department Visit: Development and Validation of Measures.

STUDY OBJECTIVE: This study aims to develop and validate measures of experiences of an emergency department (ED) visit suitable for use by older adults or their family members. METHODS: A cohort of patients aged 75 years and older who were discharged home was recruited at 4 EDs. At 1 week after the visit, patients or family members were interviewed by telephone to assess problems experienced at the visit. Twenty-six questions based on 6 domains of care found in the literature were developed: 16 questions were administered to all patients; 10 questions were administered to bed patients only. Scales were developed with multiple correspondence analysis. Regression analyses were used to validate the scales, using 2 validation criteria: perceived overall quality of care and willingness to return to the same ED. RESULTS: Four hundred twelve patients completed the 1-week interview, 197 ambulatory and 215 bed patients; family members responded for 75 patients. Two scales were developed, assessing personal care and communication (8 questions; α=.63) and waiting times (2 questions; α=.79). Both scales were significantly independently associated with perceived overall quality of care and willingness to return to the same ED. CONCLUSION: Two scales assessing important aspects of ED care experienced by older adults are ready for further evaluation in other settings.

α-Amylase Mediates Host Acceptance in the Braconid Parasitoid Cotesia flavipes.

Foraging parasitoids use chemical signals in host recognition and selection processes. Although, the volatiles play a relevant role in the localization by parasitoids of their hosts feeding on plants, the host identification process for acceptance occurs mainly during contact between the parasitoid and its host where host products related to feeding activities, fecal pellets and oral secretions, play a crucial role. The purpose of this study was to identify the nature of the contact kairomone(s) that mediate the acceptance for oviposition of the parasitoid Cotesia flavipes Cameron (Hymenoptera, Braconidae), which was released in Kenya in 1993 to control the invasive crambid Chilo partellus (Swinhoe). Using host and non-hosts of C. flavipes, we showed that it is mainly the oral secretions of the larvae that harbour the active compound(s) that mediate host acceptance for oviposition by C. flavipes. Using an integration of behavioral observations and biochemical approaches, the active compound of the oral secretions was identified as an α-amylase. Using synthetized α-amylases from Drosophila melanogaster (an insect model for which syntheses of active and inactive α-amylases are available), we observed that the conformation of the enzyme rather than its catalytic site as well as its substrate and its degradation product is responsible for host acceptance and oviposition mediation of C. flavipes females. The results suggest that the α-amylase from oral secretions of the caterpillar host is a good candidate for an evolutionary solution to host acceptance for oviposition in C. flavipes.

Twelve months of implementation of health care performance-based financing in Burkina Faso: A qualitative multiple case study.

To improve health services' quantity and quality, African countries are increasingly engaging in performance-based financing (PBF) interventions. Studies to understand their implementation in francophone West Africa are rare. This study analysed PBF implementation in Burkina Faso 12 months post-launch in late 2014. The design was a multiple and contrasted case study involving 18 cases (health centres). Empirical data were collected from observations, informal (n = 224) and formal (n = 459) interviews, and documents. Outside the circle of persons trained in PBF, few in the community had knowledge of it. In some health centres, the fact that staff were receiving bonuses was intentionally not announced to populations and community leaders. Most local actors thought PBF was just another project, but the majority appreciated it. There were significant delays in setting up agencies for performance monitoring, auditing, and contracting, as well as in the payment. The first audits led rapidly to coping strategies among health workers and occasionally to some staging beforehand. No community-based audits had yet been done. Distribution of bonuses varied from one centre to another. This study shows the importance of understanding the implementation of public health interventions in Africa and of uncovering coping strategies.

The TLR4-TRIF pathway can protect against the development of experimental allergic asthma.

The Toll-like receptor (TLR) adaptor proteins myeloid differentiating factor 88 (MyD88) and Toll, interleukin-1 receptor and resistance protein (TIR) domain-containing adaptor inducing interferon-ß (TRIF) comprise the two principal limbs of the TLR signalling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4+ ICOS+ T cells by nasal application of Protollin™, a mucosal adjuvant composed of TLR2 and TLR4 agonists. Wild-type (WT), Trif-/- or Myd88-/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges. Protollin's protection against allergic airway disease was TRIF-dependent and MyD88-independent. TRIF deficiency diminished the CD4+ ICOS+ T-cell subsets in the lymph nodes draining the nasal mucosa, as well as their recruitment to the lungs. Overall, TRIF deficiency reduced the proportion of cervical lymph node and lung CD4+ ICOS+ Foxp3- cells, in particular. Adoptive transfer of cervical lymph node cells supported a role for Protollin-induced CD4+ ICOS+ cells in the TRIF-dependent inhibition of airway hyper-responsiveness. Hence, our data demonstrate that stimulation of the TLR4-TRIF pathway can protect against the development of allergic airway disease and that a TRIF-dependent adjuvant effect on CD4+ ICOS+ T-cell responses may be a contributing mechanism.