Stefanie Gilles

Group Leader Environmental Immunology

+49 821 400 168403 stefanie.gilles@helmholtz-muenchen.de

UK Augsburg, Administrative Building

Building / Room: 3, 034

"What makes an allergen an allergen?"

Stefanie Gilles' mission is to decipher innate immune signatures that are necessary and sufficient to break peripheral tolerance and induce allergic sensitisation. This research will help to identify novel allergens, but it could also lead to the development of allergenicity bioassays that could replace animal models in the future.

A second focus is on the immune response of the nasal mucosa under simultaneous exposure to microbes and allergens, e.g., viruses and pollen. This is relevant because humans are never exposed to "isolated" allergens or viruses under real-life conditions, but to complex, mixed bioaerosols. Therefore, it is important to study the molecular immune system in the context of co-exposure. Research on cross-signalling between infection and allergy will point to currently underestimated risk exposures.

Stefanie Gilles studied biology at the LMU. After her PhD, she worked as a postdoc on TLR signalling in human dendritic cell subsets. In 2006, Dr Gilles joined the group of Prof. Traidl-Hoffmann at ZAUM - Centre for Allergy and Environment, TUM, where she started to work with dendritic cells in the context of pollen allergies.

In 2014, she moved to Augsburg with the new Chair of Environmental Medicine, UNIKA-T, where she started as a group leader. Since 2021, she has headed the Department of Environmental Immunology of the Chair of Environmental Medicine, Faculty of Medicine, University of Augsburg. She has been associated with the Helmholtz Centre Munich as a visiting scientist since 2014 until today.

Dr. Gilles supervised 4 Bachelor's, 5 Master's, 5 PhD, and 3 MD theses and has lectured in the field of allergology in the HELENA lecture series of the HMGU. She is currently involved in setting up the Environmental Health and Lung Research School at Helmholtz Munich.

Her current team in Augsburg consists of 3 PhD students, 3 MD students, and a technician. The methods used are cell culture models, organoids, biomonitoring in human life, and experimental exposure studies.

Innate Immunity Allergic Rhinitis Respiratory Viruses Primary Cell Culture Nasal Biomarkers Dendritic Cells Pollen Human Biomonitoring Allergen Challenge Climate Change and Allergies

2021

2017

2014

2004

1999

2015 Travel Grant World Immune Regulation Meeting (WIRM)
2011 ‘Habilitation’ stipend, Science Career II, Technical University of Munich
2007 Best Oral Abstract 26th Congress of the European Academy of Allergy and Clinical Immunology (EAACI)
2005 HWP II Postdoctoral stipend Technical University of Munich

Fneish Z, Becker J, Mulenge F, Fneish F, Costa B, Traidl-Hoffmann C, Gilles S, Kalinke U.

Birch pollen-induced signatures in dendritic cells are maintained upon additional cytomegalovirus exposure During the birch pollen season an enhanced incidence of virus infections is noticed, raising the question whether pollen can affect anti-viral responses independent of allergic reactions. We previously showed that birch pollen-treatment of monocyte-derived dendritic cells (moDC) enhances human cytomegalovirus (HCMV) infection. Here we addressed how in moDC the relatively weak pollen response can affect the comparably strong response to HCMV. To this end, moDC were stimulated with aqueous birch pollen extract (APE), HCMV, and APE with HCMV, and transcriptomic signatures were determined after 6 and 24 h of incubation. Infection was monitored upon exposure of moDC to GFP expressing HCMV by flow cytometric analysis of GFP expressing cells.

Principle component analysis of RNA sequencing data revealed close clustering of mock and APE treated moDC, whereas HCMV as well as APE with HCMV treated moDC clustered separately after 6 and 24 h of incubation, respectively. Communally induced genes were detected in APE, HCMV and APE with HCMV treated moDC. In APE with HCMV treated moDC, the comparably weak APE induced signatures were maintained after HCMV exposure. In particular, NF-κB/RELA and PI3K/AKT/MAPK signaling were altered upon APE with HCMV exposure. Earlier, we discovered that NF-κB inhibition alleviated APE induced enhancement of HCMV infection. Here we additionally found that impairment of PI3K signaling reduced HCMV infection in HCMV and APE with HCMV treated moDC.

APE treated moDC that were exposed to HCMV show a unique host gene signature, which to a large extent is regulated by NF-κB activation and PI3K/AKT/MAPK signaling.

Agache I, Ricci-Cabello I, Canelo-Aybar C, Annesi-Maesano I, Cecchi L, Biagioni B, Chung KF, D'Amato G, Damialis A, Del Giacco S, De Las Vecillas L, Dominguez-Ortega J, Galán C, Gilles S, Giovannini M, Holgate S, Jeebhay M, Nadeau K, Papadopoulos N, Quirce S, Sastre J, Traidl-Hoffmann C, Walusiak-Skorupa J, Salazar J, Sousa-Pinto B, Colom M, Fiol-deRoque MA, Gorreto López L, Malih N, Moro L, Pardo MG, Pazo PG, Campos RZ, Saletti-Cuesta L, Akdis M, Alonso-Coello P, Jutel M, Akdis CA

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Ranpal S, von Bargen S, Gilles S, Luschkova D, Landgraf M, Bogawski P, Traidl-Hoffmann C, Büttner C, Damialis A, Fritsch M, Jochner-Oette S

Continental-scale evaluation of downy birch pollen production: Estimating the impacts of global change The high prevalence of hay fever in Europe has raised concerns about the implications of climate change-induced higher temperatures on pollen production. Our study focuses on downy birch pollen production across Europe by analyzing 456 catkins during 2019–2021 in 37 International Phenological Gardens (IPG) spanning a large geographic gradient. As IPGs rely on genetically identical plants, we were able to reduce the effects of genetic variability. We studied the potential association with masting behavior and three model specifications based on mean and quantile regression to assess the impact of meteorology (e.g., temperature and precipitation) and atmospheric gases (e.g., ozone (O3) and carbon-dioxide (CO2)) on pollen and catkin production, while controlling for tree age approximated by stem circumference. The results revealed a substantial geographic variability in mean pollen production, ranging from 1.9 to 2.5 million pollen grains per catkin. Regression analyses indicated that elevated average temperatures of the previous summer corresponded to increased pollen production, while higher O3 levels led to a reduction. Additionally, catkins number was positively influenced by preceding summer's temperature and precipitation but negatively by O3 levels. The investigation of quantile effects revealed that the impacts of mean temperature and O3 levels from the previous summer varied throughout the conditional response distribution. We found that temperature predominantly affected trees characterized by a high pollen production. We therefore suggest that birches modulate their physiological processes to optimize pollen production under varying temperature regimes. In turn, O3 levels negatively affected trees with pollen production levels exceeding the conditional median. We conclude that future temperature increase might exacerbate pollen production while other factors may modify (decrease in the case of O3 and amplify for precipitation) this effect. Our comprehensive study sheds light on potential impacts of climate change on downy birch pollen production, which is crucial for birch reproduction and human health.

Agache I, Annesi-Maesano I, Cecchi L, Biagioni B, Chung KF, Clot B, D'Amato G, Damialis A, Del Giacco S, Dominguez-Ortega J, Galàn C, Gilles S, Holgate S, Jeebhay M, Kazadzis S, Nadeau K, Papadopoulos N, Quirce S, Sastre J, Tummon F, Traidl-Hoffmann C, Walusiak-Skorupa J, Jutel M, Akdis CA

EAACI guidelines on environmental science for allergy and asthma: The impact of short-term exposure to outdoor air pollutants on asthma-related outcomes and recommendations for mitigation measures The EAACI Guidelines on the impact of short-term exposure to outdoor pollutants on asthma-related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence-informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short-term exposure to all pollutants evaluated increases the risk of asthma-related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of evidence at specific lag days). There is limited evidence for the impact of traffic-related air pollution and outdoor pesticides exposure as well as for the interventions to reduce emissions. Due to the quality of evidence, conditional recommendations were formulated for all pollutants and for the interventions reducing outdoor air pollution. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but global measures for clean air are needed to achieve significant impact.

Agache I, Canelo-Aybar C, Annesi-Maesano I, Cecchi L, Biagioni B, Chung F, D'Amato G, Damialis A, Del Giacco S, De Las Vecillas L, Dominguez-Ortega J, Galàn C, Gilles S, Giovannini M, Holgate S, Jeebhay M, Nadeau K, Papadopoulos N, Quirce S, Sastre J, Traidl-Hoffmann C, Walusiak-Skorupa J, Sousa-Pinto B, Salazar J, Rodríguez-Tanta LY, Cantero Y, Montesinos-Guevara C, Song Y, Alvarado-Gamarra G, Sola I, Alonso-Coello P, Nieto-Gutierrez W, Jutel M, Akdis CA

The impact of indoor pollution on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new-onset asthma (incidence) and (ii) adverse asthma-related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new-onset asthma and critical and important asthma-related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact). Exposure to damp/mould increases the risk of new-onset wheeze (moderate certainty evidence). Exposure to cleaning agents may be associated with a higher risk of new-onset asthma and with asthma severity (low level of certainty). Exposure to pesticides and VOCs may increase the risk of new-onset asthma (very low certainty evidence). The impact on asthma-related outcomes of all major indoor pollutants is uncertain. As the level of certainty is low or very low for most of the available evidence on the impact of indoor pollutants on asthma-related outcomes more rigorous research in the field is warranted.

Ranpal S, von Bargen S, Gilles S, Luschkova D, Landgraf M, Traidl-Hoffmann C, Büttner C, Damialis A, Jochner-Oette S

Pollen production of downy birch (Betula pubescens Ehrh.) along an altitudinal gradient in the European Alps High-altitude environments are highly susceptible to the effects of climate change. Thus, it is crucial to examine and understand the behaviour of specific plant traits along altitudinal gradients, which offer a real-life laboratory for analysing future impacts of climate change. The available information on how pollen production varies at different altitudes in mountainous areas is limited. In this study, we investigated pollen production of 17 birch (Betula pubescens Ehrh.) individuals along an altitudinal gradient in the European Alps. We sampled catkins at nine locations in the years 2020–2021 and monitored air temperatures. We investigated how birch pollen, flowers and inflorescences are produced in relation to thermal factors at various elevations. We found that mean pollen production of Betula pubescens Ehrh. varied between 0.4 and 8.3 million pollen grains per catkin. We did not observe any significant relationships between the studied reproductive metrics and altitude. However, minimum temperature of the previous summer was found to be significantly correlated to pollen (rs = 0.504, p = 0.039), flower (rs = 0.613, p = 0.009) and catkin (rs = 0.642, p = 0.005) production per volume unit of crown. Therefore, we suggest that temperature variability even at such small scales is very important for studying the response related to pollen production.

Bayr D, Plaza MP, Gilles S, Kolek F, Leier-Wirtz V, Traidl-Hoffmann C, Damialis A

Pollen long-distance transport associated with symptoms in pollen allergics on the German Alps: An old story with a new ending? Pollen grains are among the main causes of respiratory allergies worldwide and hence they are routinely monitored in urban environments. However, their sources can be located farther, outside cities' borders. So, the fundamental question remains as to how frequent longer-range pollen transport incidents are and if they may actually comprise high-risk allergy cases. The aim was to study the pollen exposure on a high-altitude location where only scarce vegetation exists, by biomonitoring airborne pollen and symptoms of grass pollen allergic individuals, locally. The research was carried out in 2016 in the alpine research station UFS, located at 2650 m height, on the Zugspitze Mountain in Bavaria, Germany. Airborne pollen was monitored by use of portable Hirst-type volumetric traps. As a case study, grass pollen-allergic human volunteers were registering their symptoms daily during the peak of the grass pollen season in 2016, during a 2-week stay on Zugspitze, 13-24 June. The possible origin of some pollen types was identified using back trajectory model HYSPLIT for 27 air mass backward trajectories up to 24 h. We found that episodes of high aeroallergen concentrations may occur even at such a high-altitude location. More than 1000 pollen grains m-3 of air were measured on the UFS within only 4 days. It was confirmed that the locally detected bioaerosols originated from at least Switzerland, and up to northwest France, even eastern American Continent, because of frequent long-distance transport. Such far-transported pollen may explain the observed allergic symptoms in sensitized individuals at a remarkable rate of 87 % during the study period. Long-distance transport of aeroallergens can cause allergic symptoms in sensitized individuals, as evidenced in a sparse-vegetation, low-exposure, 'low-risk' alpine environment. We strongly suggest that we need cross-border pollen monitoring to investigate long-distance pollen transport, as its occurrence seems both frequent and clinically relevant.

Gilles S, Meinzer M, Landgraf M, Kolek F, von Bargen S, Pack K, Charalampopoulos A, Ranpal S, Luschkova D, Traidl-Hoffmann C, Jochner-Oette S, Damialis A, Büttner C

Betula pendula trees infected by birch idaeovirus and cherry leaf roll virus: Impacts of urbanisation and NO2 levels Viruses are frequently a microbial biocontaminant of healthy plants. The occurrence of the infection can be also due to environmental stress, like urbanisation, air pollution and increased air temperature, especially under the ongoing climate change. The aim of the present study was to investigate the hypothesis that worsened air quality and fewer green areas may favour the higher frequency of common viral infections, particularly in a common tree in temperate and continental climates, Betula pendula ROTH.

We examined 18 trees, during the years 2015–2017, the same always for each year, in the region of Augsburg, Germany. By specific PCR, the frequency of two viruses, Cherry leaf roll virus (CLRV, genus Nepovirus, family Secoviridae), which is frequent in birch trees, and a novel virus tentatively named birch idaeovirus (BIV), which has been only recently described, were determined in pollen samples. The occurrence of the viruses was examined against the variables of urban index, air pollution (O3 and NO2), air temperature, and tree morphometrics (trunk perimeter, tree height, crown height and diameter). Generalized Non-linear models (binomial logit with backward stepwise removal of independent variables) were employed.

During the study period, both CLRV and BIV were distributed widely throughout the investigated birch individuals. CLRV seemed to be rather cosmopolitan and was present independent of any abiotic factor. BIV's occurrence was mostly determined by higher values of the urban index and of NO2. Urban birch trees, located next to high-traffic roads with higher NO2 levels, are more likely to be infected by BIV.

Increased environmental stress may lead to more plant viral infections. Here we suggest that this is particularly true for urban spaces, near high-traffic roads, where plants may be more stressed, and we recommend taking mitigation measures for controlling negative human interventions.

Buhner S, Schäuffele S, Giesbertz P, Demir IE, Zeller F, Traidl-Hoffmann C, Schemann M, Gilles S

Allergen-free extracts from birch, ragweed, and hazel pollen activate human and guinea-pig submucous and spinal sensory neurons

Schülke S, Gilles S, Jirmo AC, Mayer JU

Tissue-specific antigen-presenting cells contribute to distinct phenotypes of allergy Antigen-presenting cells (APCs) are critical cells bridging innate and adaptive immune responses by taking up, processing, and presenting antigens to naïve T cells. At steady state, APCs thus control both tissue homeostasis and the induction of tolerance. In allergies however, APCs drive a Th2-biased immune response that is directed against otherwise harmless antigens from the environment. The main types of APCs involved in the induction of allergy are dendritic cells, monocytes, and macrophages. However, these cell types can be further divided into local, tissue-specific populations that differ in their phenotype, migratory capacity, T-cell activating potential, and production of effector molecules. Understanding if distinct populations of APCs contribute to either tissue-specific immune tolerance, allergen sensitization, or allergic inflammation will allow us to better understand disease pathology and develop targeted treatment options for different stages of allergic disease. Therefore, this review describes the main characteristics, phenotypes, and effector molecules of the APCs involved in the induction of allergen-specific Th2 responses in affected barrier sites, such as the skin, nose, lung, and gastrointestinal tract. Furthermore, we highlight open questions that remain to be addressed to fully understand the contribution of different APCs to allergic disease.

PD Dr. Stefanie Gilles

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Fields of Work and Expertise

Professional Career

Group leader Environmental Immunology, Environmental Medicine, Faculty of Medicine, University of Augsburg

Habilitation in Experimental Allergology at the Technical University of Munich

Group leader Environmental Immunology, Chair of Environmental Medicine, UNIKA-T, Technical University of Munich

PhD at Ludwig Maximilian University of Munich

Diploma in Biology at Ludwig Maximilian University of Munich

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