Mechanism decoded: How farm bacteria protect from asthma and allergies

Microscopic image of two dendritic cells (shades of grey), endosomes (green) and DNA (red). The two red areas represent the cell nuclei, red dots in the periphery are bacterial DNA. Some bacteria are incorporated in endosomes (arrow). (Photo: K. Stein/FZB)

Children growing up in the countryside – especially on traditional farms – have a lower risk of getting asthma in their later life. The so-called hygiene hypothesis states that substances of this “dirtier” rural environment influence the child’s immune system in a way that prohibits responses against otherwise harmless substances such as pollen. Scientists from the Research Center Borstel found a mechanism that supports this hypothesis.  

For more than 20 years it is known from epidemiological studies that children being raised on farms bear a lower risk to suffer from allergies and asthma compared to children from cities (‘farm effect’). In comparison to healthy subjects, the immune system of asthmatics is shifted towards a so-called Th2 response (in contrast to the allergy-protecting Th1 response). Both types of responses are characterized by special T-helper cells and cytokines that play a distinct role in protecting us from different kinds of pathogens. The immune system of a newborn infant is polarized towards Th2 reactions. However, in the course of the first months of its life a natural balance of Th1 and Th2 response develops. Which is the cause of this shift? Most probably these are influences that children experience on traditional farms. There is evidence that substances from food (raw cow milk, e.g.) as well as bacteria from the rural environment have a protective effect.
Dr. Karina Stein, Prof. Dr. Holger Heine and colleagues from the Research Center Borstel just published results of a study in the Journal of Allergy and Clinical Immunology that takes a close look at the bacterium Lactococcus lactis G121. In earlier studies, this microbe found in cowsheds showed an allergy-protective effect. If these – for humans harmless – bacteria end up in the human body, they are incorporated by dendritic cells. These cells play an important role in the immune system: They take up substances from their environment and process them in order to initiate a proper reaction of the immune system. Hence, the immune system is polarized in the direction of a Th1 or a Th2 response.
The scientists from Borstel investigated how bacterial compounds promote Th1 responses and therefore have an allergy-protective effect. After being taken up by dendritic cells, Lactococcus bacteria are fragmented inside of so-called endosomes. The scientists show in the journal paper that ribonucleic acids (RNAs) from the bacteria are crucial for the Th1 polarizing, protective effect: RNAs bind to distinct Toll like receptors which trigger the dendritic cells to secrete a distinct set of cytokines. These cytokines bind to T cells and polarize them in the direction of a Th1 response. In an animal model, an allergic reaction was suppressed when mice were treated with Lactococcus. „Earlier studies found that parts of the bacterial cell wall contribute to the ‘farm effect’”, explains Holger Heine, Head of the Research Group Innate Immunity in Borstel. “In the case of the mechanism we described in the paper, Lactococcus bacteria have to be taken up on the whole and fragmented afterwards. Only after this processing RNAs can be effective in polarization of the immune response. Obviously, a certain diversity, a mixture of different micro-organisms and parts of them has an effect on the child’s immune system and protects from asthma and allergies.” A future project of the group of Holger Heine is the full elucidation of all players involved in the mechanism of this effect.

Further information:
Stein, K, Brand S, Jenckel A, Sigmund A, Chen ZJ, Kirschning CJ, Kauth M, Heine H. 2016. Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects. Journal of Allergy and Clinical Immunology. [Epub ahead of print]




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