Prof. Dr. Claudia Traidl-Hoffmann

2013 PLOS ONE

Beck I, Jochner S, Gilles S, McIntyre M, Buters JT, Schmidt-Weber C, Traidl-Hoffman C, et al.

High environmental ozone levels lead to enhanced allergenicity of birch pollen

Evidence is compelling for a positive correlation between climate change, urbanisation and prevalence of allergic sensitisation and diseases. The reason for this association is not clear to date. Some data point to a pro-allergenic effect of anthropogenic factors on susceptible individuals. To evaluate the impact of urbanisation and climate change on pollen allergenicity. Catkins were sampled from birch trees from different sites across the greater area of Munich, pollen were isolated and an urbanisation index, NO2 and ozone exposure were determined. To estimate pollen allergenicity, allergen content and pollen-associated lipid mediators were measured in aqueous pollen extracts. Immune stimulatory and modulatory capacity of pollen was assessed by neutrophil migration assays and the potential of pollen to inhibit dendritic cell interleukin-12 response. In vivo allergenicity was assessed by skin prick tests. The study revealed ozone as a prominent environmental factor influencing the allergenicity of birch pollen. Enhanced allergenicity, as assessed in skin prick tests, was mirrored by enhanced allergen content. Beyond that, ozone induced changes in lipid composition and chemotactic and immune modulatory potential of the pollen. Higher ozone-exposed pollen was characterised by less immune modulatory but higher immune stimulatory potential. It is likely that future climate change along with increasing urbanisation will lead to rising ozone concentrations in the next decades. Our study indicates that ozone is a crucial factor leading to clinically relevant enhanced allergenicity of birch pollen. Thus, with increasing temperatures and increasing ozone levels, also symptoms of pollen allergic patients may increase further.

2021 PNAS

Damialis A, Gilles S, Sofiev M, Sofieva V, Kolek F, Bayr D, Traidl-Hoffman C, et al.

Higher airborne pollen concentrations correlated with increased SARS-CoV-2 infection rates, as evidenced from 31 countries across the globe

Pollen exposure weakens the immunity against certain seasonal respiratory viruses by diminishing the antiviral interferon response. Here we investigate whether the same applies to the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is sensitive to antiviral interferons, if infection waves coincide with high airborne pollen concentrations. Our original hypothesis was that more airborne pollen would lead to increases in infection rates. To examine this, we performed a cross-sectional and longitudinal data analysis on SARS-CoV-2 infection, airborne pollen, and meteorological factors. Our dataset is the most comprehensive, largest possible worldwide from 130 stations, across 31 countries and five continents. To explicitly investigate the effects of social contact, we additionally considered population density of each study area, as well as lockdown effects, in all possible combinations: without any lockdown, with mixed lockdown-no lockdown regime, and under complete lockdown. We found that airborne pollen, sometimes in synergy with humidity and temperature, explained, on average, 44% of the infection rate variability. Infection rates increased after higher pollen concentrations most frequently during the four previous days. Without lockdown, an increase of pollen abundance by 100 pollen/m3 resulted in a 4% average increase of infection rates. Lockdown halved infection rates under similar pollen concentrations. As there can be no preventive measures against airborne pollen exposure, we suggest wide dissemination of pollen-virus coexposure dire effect information to encourage high-risk individuals to wear particle filter masks during high springtime pollen concentrations.

2008 Journal of Investigative Dermatology

Eyerich K, Foerster S, Rombold S, Seidl HP, Behrendt H, Hofmann H, Traidl-Hoffman C, et al.

Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22

Chronic mucocutaneous candidiasis (CMC) constitutes a selective inability to clear infection with the yeast Candida, resulting in persistent debilitating inflammation of skin, nails, and mucous membranes. The underlying defect is unknown. Only recently, IL-17-producing T cells have been reported to be involved in clearing Candida infections. In order to characterize T cellular immune response to Candida, we analyzed T-cell cytokine secretion to Candida antigen and mitogenic stimuli in CMC patients, immunocompetent patients suffering from acute Candida infection, and healthy volunteers. Peripheral blood mononuclear cells (PBMCs) from CMC patients produced significantly lower amounts of IL-17 and IL-22 mRNA and protein when stimulated with Candida albicans or mitogen in vitro compared with that in matched healthy individuals. Additionally, PBMCs from immunocompetent Candida-infected patients secreted more IL-17 and IL-22 than those of both CMC patients and healthy, non-infected controls. Flow cytometry revealed a decreased number of CCR6+ IL-17-producing T cells in CMC patients, whereas the amount of CCR6+/CCR4+ cells was not altered. Levels of differentiating cytokines for human Th17 cells, IL-1β and IL-6, tended to be higher in CMC patients. The inability to clear C. albicans in CMC patients could be due to a defect in the immune response of IL-17-producing T cells.

2020 Allergy

Gilles S, Blume C, Wimmer M, Damialis A, Meulenbroek L, Gökkaya M, Traidl-Hoffman C, et al.

Pollen exposure weakens innate defense against respiratory viruses

Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non-allergic patients frequently present to doctors with severe respiratory tract infections. Our objective was therefore to assess whether pollen may interfere with antiviral immunity.

2009 The Journal of Immunology

Gilles S, Mariani V, Bryce M, Mueller MJ, Ring J, Jakob T, Traidl-Hoffman C, et al.

Pollen-derived E1-phytoprostanes signal via PPAR-gamma and NF-kappaB-dependent mechanisms

In a humid milieu such as mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators. Among these, the E1-phytoprostanes (PPE1) were identified to modulate dendritic cell (DC) function: PPE1 inhibit the DC’s capacity to produce IL-12 and enhance DC mediated TH2 polarization of naive T cells. The mechanism(s) by which PPE1 act on DC remained elusive. We thus analyzed candidate signaling elements and their role in PPE1-mediated regulation of DC function. Aqueous birch pollen extracts induced a marked cAMP response in DC that could be blocked partially by EP2 and EP4 antagonists. In contrast, PPE1 hardly induced cAMP and the inhibitory effect on IL-12 production was mostly independent of EP2 and EP4. Instead, PPE1 inhibited the LPS-induced production of IL-12 p70 by a mechanism involving the nuclear receptor PPAR-γ. Finally, PPE1 efficiently blocked NF-κB signaling in DCs by inhibiting IκB-α degradation, translocation of p65 to the nucleus, and binding to its target DNA elements. We conclude that pollen-derived PPE1 modulate DC function via PPAR-γ dependent pathways that lead to inhibition of NFκB activation and result in reduced DC IL-12 production and consecutive TH2 polarization.

2019 International Archives of Allergy and Immunology

Harter K, Hammel G, Krabiell L, Linkohr B, Peters A, Schwettmann L, Traidl-Hoffman C, et al.

Different Psychosocial Factors Are Associated with Seasonal and Perennial Allergies in Adults: Cross-Sectional Results of the KORA FF4 Study

Background: Psychosocial factors are supposed to play a central role in the development of allergic diseases. Associations with seasonal and perennial forms of allergies have not been investigated, yet. Objectives: The aim of the study was to investigate the associations of psychosocial factors (social status, depression, generalized anxiety, psychosocial stress, Type-D personality) with seasonal, perennial, and other forms of allergies in adults. Method: The analysis of self-reported data of the KORA FF4 study was performed with SAS 9.4. The sample consisted of 1,782 study participants in the study region of Augsburg (39–88 years, 61 years, 51.1% female). Descriptive bivariate statistics and multinomial logistic regression models were performed. Age, sex, family predisposition, and smoking status were considered possible confounders. Moreover, several sensitivity analyses were carried out to check whether missing values distorted the results. Results: A positive association between generalized anxiety and seasonal allergies was found in the multivariate model. Depression was positively, and anxiety negatively, associated with perennial allergies. No association between the analyzed psychosocial factors and other forms of allergies could be found. Conclusion: The results support the relevance of psychosocial factors in association with allergies. Looking at the psychosocial factors, a separate consideration of seasonal and perennial allergies seems reasonable. Further longitudinal studies should investigate the direction of the associations, the underlying mechanisms, and other psychosocial factors, such as coping mechanisms, in confirmed allergies.

2022 The Lancet Planetary Health

Herrmann A, Lenzer B, Müller BS, Danquah I, Nadeau KC, Muche-Borowski C, Traidl-Hoffmann C, et al.

Integrating planetary health into clinical guidelines to sustainably transform health care

Climate change and other ecological crises threaten the health of humans and the natural systems on which humans depend.1 However, such planetary health issues have not yet entered the core of evidence-based medicine—clinical guidelines. Globally, medical associations, research institutions, and universities have placed planetary health on their agenda and are starting to integrate it into medical education.2, 3 The UK National Health Service (NHS) aims to be climate neutral by 2040,4 and more than 50 countries committed to climate-smart health care by 2030 at the 26th UN Climate Conference of the Parties in Glasgow, Scotland.5 Despite all this progress, planetary health principles have yet to be fully incorporated into clinical routines. To achieve this, we believe that clinical guidelines are crucial. We screened a sample of 49 clinical guidelines from British, Chinese, Indian, Brazilian, Australian, European, German, and US-American medical associations and organisations (appendix pp 1–8). We selected guidelines dealing with a range of topics, which have apparent associations with planetary health issues, such as allergies, asthma, chronic obstructive pulmonary disease, cardiovascular disease, obesity, diabetes, dermatology, renal diseases, heat stroke, and colorectal cancer. We used the QDA Miner Lite programme (version 2.0.7; Provalis Research) to scan the guidelines for 30 keywords related to planetary health (eg, climate change, air pollution, and emissions; appendix pp 8–10). Most of the keywords were found in fewer than 5% of the guidelines. As an exception, “air pollution” was mentioned in 20%, and “environmental protection” and “emissions” in 10% of the scanned guidelines. If any of the 30 keywords were mentioned, they were frequently used in the context of disease aetiology or epidemiology and less often with regards to sustainable health services. Notably, the scanned British clinical practice guidelines from the National Institute for Health and Care Excellence (NICE) include an introductory paragraph about responsibility to promote environmentally sustainable health care. The NICE guideline on the prevention of cardiovascular disease explicitly mentions the environmental cobenefits of physically active travel and reduced intakes of animal-based saturated fats.6 The NICE strategy for 2021 to 2026 aims to develop a framework that aids in including environmental impact data in their guidelines to reduce the environmental footprint of health care.7 We argue that all medical associations and organisations who publish medical guidelines should include a strategy that systematically addresses planetary health issues in their guidelines. WHO has developed recommendations on how to incorporate equity, human rights, gender, and social determinants of health as cross-cutting issues into each step of WHO guideline development.8 Similarly, planetary health should become a mandatory dimension of clinical guideline development. The panel shows in what areas of guidelines the planetary health dimension should be considered. Developing separate guidelines on specific sustainable health care topics could also be useful—eg, administration of climate-friendly anaesthesia.

2020 Allergy

Hülpüsch C, Tremmel K, Hammel G, Bhattacharyya M, de Tomassi A, Nussbaumer T, Traidl-Hoffman C, et al.

Skin pH-dependent Staphylococcus aureus abundance as predictor for increasing atopic dermatitis severity

Background Atopic eczema (atopic dermatitis, AD) is characterized by disrupted skin barrier associated with elevated skin pH and skin microbiome dysbiosis, due to high Staphylococcus aureus loads, especially during flares. Since S aureus shows optimal growth at neutral pH, we investigated the longitudinal interplay between these factors and AD severity in a pilot study. Method Emollient (with either basic pH 8.5 or pH 5.5) was applied double-blinded twice daily to 6 AD patients and 6 healthy (HE) controls for 8 weeks. Weekly, skin swabs for microbiome analysis (deep sequencing) were taken, AD severity was assessed, and skin physiology (pH, hydration, transepidermal water loss) was measured. Results Physiological, microbiome, and clinical results were not robustly related to the pH of applied emollient. In contrast to longitudinally stable microbiome in HE, S aureus frequency significantly increased in AD over 8 weeks. High S aureus abundance was associated with skin pH 5.7-6.2. High baseline S aureus frequency predicted both increase in S aureus and in AD severity (EASI and local SCORAD) after 8 weeks. Conclusion Skin pH is tightly regulated by intrinsic factors and limits the abundance of S aureus. High baseline S aureus abundance in turn predicts an increase in AD severity over the study period. This underlines the importance and potential of sustained intervention regarding the skin pH and urges for larger studies linking skin pH and skin S aureus abundance to understand driving factors of disease progression.

2021 Allergy

Hülpüsch C, Weins AB, Traidl-Hoffmann C, Reiger M

A new era of atopic eczema research: Advances and highlights

Atopic eczema (AE) is an inflammatory skin disease with involvement of genetic, immunological and environmental factors. One hallmark of AE is a skin barrier disruption on multiple, highly interconnected levels: filaggrin mutations, increased skin pH and a microbiome dysbiosis towards Staphylococcus aureus overgrowth are observed in addition to an abnormal type 2 immune response. Extrinsic factors seem to play a major role in the development of AE. As AE is a first step in the atopic march, its prevention and appropriate treatment are essential. Although standard therapy remains topical treatment, powerful systemic treatment options emerged in the last years. However, thorough endotyping of the individual patients is still required for ideal precision medicine approaches in future. Therefore, novel microbial and immunological biomarkers were described recently for the prediction of disease development and treatment response. This review summarizes the current state of the art in AE research.

2007 The Journal of Immunology

Mariani V, Gilles S, Jakob T, Thiel M, Mueller MJ, Ring J, Traidl-Hoffman C, et al.

Immunomodulatory mediators from pollen enhance the migratory capacity of dendritic cells and license them for Th2 attraction

The immune response of atopic individuals against allergens is characterized by increased levels of Th2 cytokines and chemokines. However, the way in which the cytokine/chemokine profile is matched to the type of invading allergen, and why these profiles sometimes derail and lead to disease, is not well understood. We recently demonstrated that pollen modulates dendritic cell (DC) function in a way that results in an enhanced capacity to initiate Th2 responses in vitro. Here, we examined the effects of aqueous birch pollen extracts (Bet.-APE) on chemokine receptor expression and chemokine production by human monocyte-derived DCs. Bet.-APE strongly induced expression and function of CXCR4 and reduced CCR1 and CCR5 expression on immature DCs. In addition, DC treatment with Bet.-APE significantly reduced LPS-induced production of CXCL10/IP-10, CCL5/RANTES; induced CCL22/macrophage-derived chemokine; and did not significantly change release of CCL17/thymus and activation-regulated chemokine. At a functional level, Bet.-APE increased the capacity of LPS-stimulated DCs to attract Th2 cells, whereas the capacity to recruit Th1 cells was reduced. Bet.-APE significantly and dose-dependently enhanced intracellular cAMP, suggesting that water-soluble factors from pollen grains bind a Gαs-protein-coupled receptor. E1-Phytoprostanes were identified to be one player in the Th2-polarizing potential of aqueous pollen extracts. In summary, our results demonstrate that pollen itself releases regulatory mediators which generate a Th2-promoting micromilieu with preferential recruitment of Th2 cells to the site of pollen exposure.