Environmental Immunology

Research on Allergy Initiators

Allergies have become a true epidemic in western civilizations. Allergic patients suffer considerably from the symptoms of hay fever (allergic rhinitis), allergic conjunctivitis, eczema, and For_Umw_Imm_DC.5asthma. People affected from allergies are compromised in their quality of life as well as in their performance at work and in school.

Therefore, allergies cause a strong socio-economic burden.The most important outdoor allergens are pollen from amenophilic plants such as trees, grasses, and weeds. Within the research area of environmental immunology at the Institute of Environmental Medicine (IEM), UNIKA-T, under the guidance of Professor Claudia Traidl-Hoffmann, the focus is on answering the following key questions:

  1. How do environmental factors like microbial burden, air pollutants, urbanization, and climate change-related factors impact pollen-producing plants and thus influence the allergenicity of pollen?
  2. How do plant pollen and the human immune system interact with each other - which then induces an allergic immune response to “harmless” pollen antigens?

The Axis Environment –Allergenic Plant – Human

Both the climate change and an exposure to air pollutants impact directly and indirectly on the expression of allergic diseases. In a recent study, we could demonstrate that those birch trees which grow under elevated ozone exposure produce pollen that cause even more severe symptoms in allergic patients than usual pollen.

In a current project funded by the Helmholtz Environmental Health program, we analyze how pollen from common ragweed (Ambrosia artemisiifolia), a spreading neophyte in eastern and central Europe, is influenced by air pollutants factors of the climate change, such as drought stress, ozone, and elevated CO2.

Therefore, pollen is isolated from Ambrosia plants, which are being cultivated in climate chambers under defined environmental conditions. This pollen is then tested for its immune modulatory potential in different cell culture models (human dendritic cells, primary nasal epithelial cells, neutrophils and eosinophils, murine B cells). Allergenicity of the pollen samples is assessed in clinical tests on allergic patients, i. e. skin prick tests and nasal challenges.

Pollen (photo: IEM)

Pollen (photo: IEM)

Cross-kingdom Signaling – Communication Between Plant Pollen and the Human Immune System

The “default” reaction of the human immune system to pollen exposure is tolerance. This means that the immune system learns to specifically tolerate pollen proteins. Why this process of active toleration fails to work in allergic patients is still incompletely researched. Genetic predisposition plus environmental and life style factors are supposed to act together in a process ultimately leading to a loss of immunological tolerance.

The moment pollen is inhaled, it is deposited on the epithelia of the upper respiratory tract. The epithelia then transmit a signal to the associated cells of the immune system which orders either to fight or to tolerate the pollen proteins or its additional (adjuvant) substances. In the research area of Environmental Immunology, we are consequently mainly interested in answering the question how pollen and tissue cells (nasal and bronchial epithelial cells, skin keratinocytes) communicate with each other.

We additionally study how this communication affects the follow-up activation of innate and adoptive immune system cells (granulocytes, dendritic cells, T cells). Presently, we are investigating if pollen induce the inflammasome (an agent of the human immune system) in human epithelial cells. This, in combination with a lack of Th1 inducing signals, could stimulate Th2 differentiation in T cells.

In a further project, we analyze the inhibition of the innate antiviral response of epithelia caused by pollen-derived low molecular weight compounds.

Low-molecular Substances as Additional Allergy Initiators

We previously demonstrated that, along with allergen protein, pollen releases a plethora of low molecular weight substances. The latter are non-allergenic by themselves but can skew the For_Umw_Imm_Nasenepithel.7immune system towards an allergic response.

These substances include the pollen-associated lipid mediators (PALMs), derivatives of linoleic and linolenic acid, which are structurally and functionally homologous to mammalian leukotrienes and prostaglandins. They can attract and activate innate immune cells like neutrophils and eosinophils, or modulate the function of dendritic cells in such a way that they are unable to differentiate Th1 cells. This, in turn, might promote the differentiation of allergy relevant Th2 cells.

In addition to PALMs, pollen releases immunologically and neurologically active compounds such as adenosine. In human dendritic cell cultures, adenosine seems tolerance stimulating, whereas cells derived from allergic donors were unable to sense this allergy-protective signal correctly. Possibly, however, adenosine is still not a “good guy” after all, but even exacerbates an allergic disease in already sensitized patients.

Whether this is correct or not is presently under investigation in an experimental model on pollen allergy. Because pollen produces such high numbers of potentially bioactive substances, we aim at identifying those responsible for most of the observed immunological effects. To reach this goal, metabolome approaches are a key technological tool, followed by chromatographic separation techniques, in vitro cell culture tests and finally by human studies such as nasal provocation and skin prick tests.

Nasal epithelium (photo: IEM)

Nasal epithelium (photo: IEM)

Collaborations

  • Institute for Biochemical Plant Pathology (BIOP), Helmholtz Zentrum München
  • Research Unit Analytical BioGeoChemistry (BGC), Helmholtz Zentrum München
  • Immunopharmacology, Utrecht University (NL)
  • ENT Department, Klinikum Rechts der Isar, Technical University of Munich
  • Department of Dermatology and Allergy, Klinikum Rechts der Isar, Technical University of Munich
  • Cellular and Molecular Allergology, University of Salzburg (A)
  • Department of Pathophysiology, Infectiology and Immunology, Medical University of Vienna (A)
  • Biocentre Würzburg