Proteolytic activity in cowshed dust extracts induces C5a release in murine bronchoalveolar lavage fluids which may account for its protective properties in allergic airway inflammation

Stiehm, Matthias; Bufe, Albrecht; Peters, Marcus

doi:10.1136/thoraxjnl-2012-201746

Cited by 15 publications

(8 citation statements)

References 30 publications

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“…Furthermore, a recent study shows that cowshed dust extract activates C5a production and that C5a, when administered during the sensitization, dampens the allergic asthma phenotype in a mouse model. 71 In contrast, C5aR1 targeting in an established allergic environment led to a reduction in airway inflammation and AHR was still associated with increased production of Th2 effector cytokines. 14,72 Finally, C5aR2-deficiency protects from AHR, Th2 cytokine production, serum IgE secretion, mucus production, 73 and inflammatory cell infiltration.…”

Section: Anaphylatoxin-mediated Regulation Of Allergen Sensitizationmentioning

confidence: 99%

Old dogs—new tricks: immunoregulatory properties of C3 and C5 cleavage fragments

Verschoor

Karsten

Broadley

et al. 2016

Immunological Reviews

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The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes. In the circulation, it also facilitates the transport and delivery of bacteria and immune complexes to phagocytes, through a process known as immune adherence, with consequences for adaptive immunity. Here, we will discuss non-classical immunoregulatory properties of C3 and C5 cleavage fragments. We highlight the influence of anaphylatoxins on Th2 and Th17 cell development during allergic asthma with a particular emphasis on their role in the modulation of CD11b conventional dendritic cells and monocyte-derived dendritic cells. Furthermore, we discuss the control of anaphylatoxin-mediated activation of dendritic cells and allergic effector cells by adaptive immune mechanisms that involve allergen-specific IgG1 antibodies and plasma or regulatory T cell-derived IL-10 production. Finally, we take a fresh look at immune adherence with a particular focus on the development of antibacterial cytotoxic T-cell responses.

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Section: Anaphylatoxin-mediated Regulation Of Allergen Sensitizationmentioning

confidence: 99%

Old dogs—new tricks: immunoregulatory properties of C3 and C5 cleavage fragments

Verschoor

Karsten

Broadley

et al. 2016

Immunological Reviews

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“…On the other hand, there are also beneficial aerosols. The beneficial farming effect has mostly been attributed to raw cow milk consumption, but also the inhalation of immune modulatory plant‐derived compounds from cowshed dust could be protective . A recent study that compared different farming and nonfarming homes in the German state of Bavaria pointed out the possible importance of environmental microbes.…”

Section: Good Dust and Bad Dust: Natural Bioaerosols Versus Anthropogmentioning

confidence: 99%

The role of environmental factors in allergy: A critical reappraisal

Gilles

Akdiş

Lauener

et al. 2018

Experimental Dermatology

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Allergies are usually referred to as type I hypersensitivity reactions against innocuous environmental antigens, characterized by a Th2/IgE-dominated inflammation. They can manifest themselves in various organs, such as skin, gastrointestinal and respiratory tract, and comprise diseases as diverse as allergic rhinitis and conjunctivitis, bronchial asthma, oral allergy syndrome, food allergy, urticaria and atopic eczema, but also anaphylactic shock. Within the last decades, there was a significant global increase in allergy prevalence, which has been mostly attributed to changes in environment and lifestyle. But which, among all factors discussed, are the most relevant, and what are the mechanisms by which these factors promote or prevent the development of allergic diseases? To answer this, it is necessary to go back to the two key questions that have occupied allergy researchers for the last decades: Firstly, what makes an allergen an allergen? Secondly, why are more and more individuals affected? Within the last decade, we have made considerable progress in answering these questions. This review gives an overview over scientific progress in the field, summarizes latest findings and points out future prospective and research needs.

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“…Accordingly, various farm‐associated exposures were differentially analyzed in association studies , and components of all these sources have been taken into account in the search for potential causative substances. Starting from extracts of cowshed dust , such differing substances as arabinogalactan (a high molecular weight plant sugar) , and a serine protease from the mealworm (the larva of the beetle Tenebrio molitor ) have been demonstrated to protect from allergic sensitization and/or inflammation in appropriate mouse models. The inverse relation of endotoxin levels in children mattress dusts to the occurrence of hay fever, atopic asthma, and atopic sensitization spurred studies focussing on the microflora of the farming environment.…”

Section: The Specific Nature Of the Farming Environmentmentioning

confidence: 99%

Allergy protection by cowshed bacteria – recent findings and future prospects

Kauth¹,

Heine

2016

Pediatric Allergy Immunology

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Since the first publication in 1999, numerous epidemiologic studies provided strong evidence that frequent contact to a traditional farm environment in early life protects children from the development of allergic airway diseases. These consistent findings prompted enormous efforts to identify and characterize the potential causative factors and the underlying immunologic mechanisms in experimental studies. The cumulating evidence for the role of the cowshed-associated bacterial flora led to enhanced efforts not only to identify the relevant species but also to examine their specific immunomodulatory capacity, the bacterial components involved, and particularly the cellular and molecular mechanisms of their interaction with the immune system. We review here the methods applied to identify relevant bacterial species, the species which emerged thereof, and the similarities and differences in their mode of action as revealed so far. We further consider the impact of the current knowledge on worthwhile clinical application and reflect on the required next steps to foster the translation of the encouraging scientific progress which has been made in recent years.

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Proteolytic activity in cowshed dust extracts induces C5a release in murine bronchoalveolar lavage fluids which may account for its protective properties in allergic airway inflammation

Cited by 15 publications

References 30 publications

Old dogs—new tricks: immunoregulatory properties of C3 and C5 cleavage fragments

Old dogs—new tricks: immunoregulatory properties of C3 and C5 cleavage fragments

The role of environmental factors in allergy: A critical reappraisal

Allergy protection by cowshed bacteria – recent findings and future prospects

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