Special Fields at Environmental Medicine
Aerobiology (Athanasios Damialis, PhD)
Special Field - Aerobiology
Global Increase in Airborne Pollen Concentration
The scientific field of studying airborne particles is called Aerobiology. Its focus often lies on allergenic particles, i. e. pollen and fungal spores (aeroallergens). There is an increasing interest in Aerobiology because the ongoing climate change is affecting both plants and funges. Consequently, changes have been observed in the production and dispersion as well as in the allergenicity and other properties of pollen and fungal spores. In particular, pollen have been exhibiting a worldwide increase in airborne concentrations and, parallel to the latter, exacerbations in allergic diseases' frequency and severity has been documented. (Photo shows a sycamore pollen flower; photo by IEM)
The Aim is a Real-Time Allergen Monitoring
Our Aerobiology team at the Institute of Environmental Medicine, UNIKA-T, under the guidance of Professor Claudia-Traidl-Hoffmann, aims at:
1) Ongoing monitoring of pollen and fungal spores from all plants and fungal taxa respectively. This is conducted at the finest scale possible - viz. at two-hour intervals.
2) Investigation of interactions between aeroallergen concentrations and meteorological factors, with a special focus on the elaboration of aeroallergen circulation patterns and forecast models of their concentrations.
3) Developing real-time, reliable, and accurate aeroallergen measurements, which will be the basis of future evaluation of environmental risks associated with prevalent allergic symptoms.
A Fully-Automated Pollen Monitor in Action
The ultimate goal is to define thresholds of those risk factors beyond which allergic symptoms may occur. All the above aims are achieved via the use of traditional methods (volumetric particle trapping, Burkard pollen trap) plus cutting-edge infrastructure (automated pollen sampling, Hund trap). Corresponding forecasts will be achieved by a combination of aerobiological, meteorological, phenological (flowering), biological (experimental designs), clinical (patients symptoms) and otherwise collected data.
One of the most innovative research aspects is the use of cutting-edge automated pollen samplers. This provides our team with real-time and fine-scale pollen counts for the majority of those allergenic pollen types which are detected in the air. Relevant gauging results refer only to daily pollen counts at the moment, usually with a time lag of at least a week. Hence, pollen exposure of allergic patients cannot be fully avoided in advance and the current medical and pharmaceutical treatment is only partly effective. The use of above technology and its combination with traditional research findings will allow for timely, economical, efficient, and effective dissemination of the relevant data. It will furthermore guarantee the best possible management of allergic diseases by aiming at a prophylaxis rather than a follow-up treatment of patients.
Seven Activities for the Goal Achievement
The goals will be achieved by a series of activities, provisionally (but not limited to) as follows:
1) Full time operation of an automated pollen sampler (see photo on the left; photo by IEM).
2) Full time operation of two traditional aerobiological stations at ground and rooftop levels and at the finest scale possible at present - viz. at two hour intervals.
3) Combining aerobiological data with other environmental and experimental data (e. g. vegetational, meteorological) and constructing spatial and temporal forecasting models of allergenic pollen atmospheric circulation.
4) Combining environmental with medical data (e. g. symptom scores) and determining the sensitization thresholds for every pollen type and affected area.
5) Developing real-time risk alerts and information on dissemination areas via multiple channels, e. g. the UNIKA-T and TUM websites or news agencies.
6) Producing informative leaflets for an increase of public awareness - both of officially involved institutions and organizations (hospitals, health ministry etc.) and of course of the allergic patients and their physicians respectively.
7) Developing personalised cutting-edge IT technologies, mainly in the form of mobile apps, which will then inform allergic patients on the environmental risk of pollen exposure at their area either automatically or on request.
Ongoing Control and Maintenance
In order to optimize the reliability and efficiency of the novel methods above, an investigation for differences in pollen counts between traditional volumetric sampling and automated pollen sampling will be conducted first. The obtained results from both sampler types will be compared and each one´s reliability verified. Possibly occurring differences will be investigated in a qualitative (which pollen types) and quantitative analysis (how many pollen grains per type). In case of discrepancies, calibration and improvement of the respective sampler(s) will be conducted with an emphasis on the accuracy and timeliness of the obtained gauge results.
Clinical Research (Professor Claudia Traidl-Hoffmann, MD)
Information about the special field "Clinical Research" will follow soon.
Environmental Bioinformatics (Professor Avidan Neumann, PhD)
The special field "Environmental Bioinformatics" studies the interaction between environment and humans by means of bionformatical methods. Further information will follow soon.
Environmental Immunology (PD Stefanie Gilles, PhD)
Research Area - Environmental Immunology
Head of Environmental Immunology: PD Stefanie Gilles, PhD
The overall focus of our work is on the interaction of airborne allergens, such as pollen, with the innate immune system of the respiratory tract, and on the dendritic cell-mediated T cell response. Of special interest is the question, which signals have to be delivered by innocuous foreign proteins in order to be erroneously recognized by the mammalian immune system as harmful, so that peripheral tolerance is broken and allergic sensitization is initiated. It is the key question in allergy research that is only just beginning to be understood: What makes an allergen an allergen? Recent research, mainly on house dust mite allergens, has highlighted the role of innate immune activation as prerequisite for allergic sensitization. I am especially interested in finding out whether there is there a specific signaling pattern mediated by receptors of the innate immune system that paves the way for allergic sensitization (see figure 1).
Figure 1: Research at the lab group of Environmental Immunology
(Click on the image for an enlarged view.)
Most of our recent and ongoing work focuses on pollen. This is first of all due to the fact that pollen grains are among the most relevant allergen carriers in outdoor air, and allergic rhinitis to pollen is very frequent in developed countries. But pollen grains are also an interesting model to search for common signaling features shared by many (or differing between) allergens. Interestingly, most of the allergenic proteins from pollen that are known to date do not trigger the innate immune system by themselves. This is in contrast to major allergens from house dust mite, some of which directly engage and activate pattern recognition receptors, e.g. DC-SIGN, or act as co-ligands for such receptors, e.g. TLR4. Therefore, the comparison between immune responses to isolated pollen proteins, total and fractionated pollen extracts can help to identify receptors and downstream signaling events that might trigger or facilitate allergic sensitization. In the past we discovered pollen-associated lipid mediators that act as chemoattractants for various innate immune cells, such as PMN, or that modulate dendritic cell function and skew the DC-mediated T helper cell response towards Th2. More recently, we identified pollen-derived adenosine as immune modulator with opposing functions, as it initially appears to transmit tolerogenic signals during the sensitization phase, but, once sensitization has occurred, exacerbates the allergic effector phase in a murine model of pollen allergy.
A more recent focus of our research is the interaction of pollen and viruses at mucosal surfaces, such as nasal epithelium (figure 2). For this we developed a technique of rapidly expanding nasal epithelial cells from small tissue samples (nasal curettages) obtained from defined donors, e.g. with allergic rhinitis to pollen, and to differentiate them in vitro into organoids (“air-liquid-interphase cultures”). These differentiated nasal epithelial cell cultures build a stable physical barrier composed of tight junctions, and they contain mucus-producing goblet cells and ciliated cells. We are presently investigating whether pollen exposure blunts the innate immune response to respiratory viruses, such as rhinovirus, HCMV and influenza A, e. g. by interfering with the virus-induced production of type I and type III interferones.
(Click on the image for an enlarged view.)
Finally, we perform long-term human biomonitoring studies to investigate how nasal and systemic immune responses evolve in healthy individuals and allergic rhinitis patients under natural pollen exposure (figure 3). Here, we are especially interested in the kinetics of nasal cytokine and immunoglobulin responses (IgE, IgG, IgA), and their relation to pollen exposure, respiratory virus occurrence and symptoms. The aim is to identify biomarkers associated with high or low symptom expression. To perform such studies, it is crucial to know as much as possible about the “real-life” exposure of the study participants. Therefore, we are continuously refining techniques to quantify nasal allergen-specific immunoglobulins, cytokines and chemokines, as well as airborne, pollen-associated and nasal microbes (bacteria and fungi). The biostatistic challenge in these projects lies in integrating complex “exposome” with complex “reactome” data, and to do this at different time-scales. In the near future, we will also look into the kinetics of evolving T cell receptor repertoires under natural pollen exposure, with focus on different CD4+ T cell subpopulations, such as Treg, Tcon and Tfh.
(Click on the image for an enlarged view.)
Heiko Adler (CPC), Ulrike Frank, Jörg Durner (BIOP), Philippe Schmitt-Kopplin (BGC), Francesca Alessandrini (IAF), Helmholtz Zentrum München
Adam Chaker (HNO Klinik, MRI TUM)
Ulrike Förster-Ruhrmann, Heidi Olze (HNO Klinik, Charite, Berlin)
Lorenz Aglas, Fatima Ferreira (Universität Salzburg)
Katarzyna Duda, Nestor Gonzales-Roldan (Forschungszentrum Borstel)
Ulrich Kalinke (Twincore, Universität Hannover)
Cezmi Akdis (SIAF, Universität Zürich, CH)
Cornelia Blume, Donna Davies (University Southampton, UK)
Johan Westin, Aslog Dahl (Universität Götheborg, Schweden)
Sebastian Johnston (Imperial College, UK)
Johan Garssen, Linda van´t Land, Laura Meulenbroek (Danone Research Group, Utrecht University, NL)
Environmental Immunology Team:
Microbiology (Matthias Reiger, PhD)
Research Area - Microbiology
There are Ten Times as many Microfolora as Human Cells
Our view of human biology and human diseases has been modified by the ongoing acquisition of knowledge about the human microbiome. Although we have always been vaguely aware that the human body is host for many microorganisms indeed, only new scientific technologies, like the DNA sequence analysis, could finally reveal in detail the vast and complex communities of microorganisms which are resident in and on the human body. It has been calculated that a human adult houses about 10 12 bacteria on the skin, 10 10 in the mouth, and 10 14 in the gastrointestinal tract. With a number of approximately 10 14 cells, the human microflora outnumbers our own body cells by factor ten. It represents thousands of bacterial, viral, and fungal species, which are all required for both normal human development and lifelong health.
(Click on the graph for an enlarged view. The graphic shows a skin profile; graphic by M. Reiger and D. Dittlein.)
Interaction Between Humans and the Environment as an Important Health Factor
Early life interactions between the developing immune system and microbes shape the outcome of our immune reactions in later life, resulting in a predisposition for or protection from allergic and autoimmune diseases. On the other hand, bacterial homeostasis on our bodies´ surfaces is constantly maintained throughout adult life, whereas an imbalance of the microbial flora can lead to a partial pathogen overgrowth.
S. Aureus Influences the Course of Atopic Dermatitis
Several lines of evidence point towards microbial involvement in the pathogenesis of atopic dermatitis (AD), a chronic relapsing disorder affecting children and adults with worldwide prevalence rates of 1-20 %. The incidence of AD has increased markedly over the past three decades, presumably also because of the influence of environmental components. The profiling of patients´ bacterial microbiota via 16S rRNA gene sequencing has confirmed increases in Staphylococcus aureus relative abundance during AD flares together with a decrease in bacterial diversity.
Which Cutaneous Dysfunctions are Worth Considering?
One aim of the microbiome research at the Institute of Environmental Medicine, is to develop better descriptions of changes in the microbiota of affected skin sites during flares of AD. This aim is realized in a large cohort study with CK-CARE at the moment. First results provide new and deeper insights into the course of flares and help clarify whether or in what way clinically different subtypes of AD vary in their respective microbiome. In this cohort study, the main focus lies on the natural course of an allergic disease to create a better understanding of the pathology of atopic eczema. The differences and similarities between the patients´ examination results will serve as a basis for further studies. The chief aim must be to elucidate the role of barrier dysfunctions and to identify whether S. aureus colonization is the cause or the result (or even both) of changes in the patients skin microbiome. Because it is known that a reduction of a S. aureus prevalence leads to a reduction of flares, we are currently researching new ways to restore each individuals normal and diverse microflora.
Bacteria and Skin Cells are Interacting
Another important aim of our microbiome team is to study the interaction between the human immune system of the skin and the microorganisms living within this environment. Skin commensal bacteria modulate skin immune cell functions and induce protective immunity to pathogens. Detecting these bacteria helps to differentiate the diversity of beneficial and pathogenic bacteria. In-vitro experiments, with the target to determine the functions of single bacteria or a set of them on human skin cells, on the other hand, leads to a fuller understanding of the respective interaction mechanisms. Changes in the microbiome during the immune system regeneration in HIV-patients are likely promising for future investigations of the interrelations between the microbiome and human cells. Our special focus is on the gut and the skin microbiome because we suspect a connection between the gut microbiota and skin health, potentially through stimulation and/or education of immune cell populations.
(Click on the graph for an enlarged view. The graphic shows the symbiosis between bacteria and skin tissue; graphic by M. Reiger and D. Dittlein.)
The Aim is the Reduction of the AD-risk
There is evidence that the gastrointestinal microbiota plays a major role in the interaction between microbiota in general and the immune system. Low diversity in the gut microbiota during early infancy has been associated with a follow-up development of atopic eczema later in life. Therefore, we involve neonates and children in our studies in order to find ways of reducing their risk of AD.
- Tom Clavel, PhD, Juniorgroup leader
- Peter Bauer, Professor
Participating Team Members:
Translational Immunology (Professor Ellen Renner, MD; Beate Hagl, PhD)
Information in English will follow soon.