Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties

Debarry, Jennifer; Garn, Holger; Hanuszkiewicz, Anna; Dickgreber, Nina; Blümer, Nicole; Mutius, Erika von; Bufe, Albrecht; Gatermann, Sören; Renz, Harald; Holst, Otto; Heine, Holger

doi:10.1016/j.jaci.2007.03.023

Cited by 250 publications

(215 citation statements)

References 43 publications

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“…Monocytes were isolated from whole blood of healthy donors, cultivated and differentiated to immature dendritic cells (iDCs) as described previously 23 with one modification: Growth factors (GM-CSF and IL4) were purchased from ImmunoTools (Friesoythe, Germany). Maturation of dendritic cells (to mDCs) was achieved by treatment with 100 ng/ml LPS from Salmonella enterica sv.…”

Section: Methodsmentioning

confidence: 99%

Epigenotype switching at the CD14 and CD209 genes during differentiation of human monocytes to dendritic cells

Bullwinkel¹,

Lüdemann²,

Debarry³

et al. 2011

Epigenetics

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Section: Methodsmentioning

confidence: 99%

Epigenotype switching at the CD14 and CD209 genes during differentiation of human monocytes to dendritic cells

Bullwinkel¹,

Lüdemann²,

Debarry³

et al. 2011

Epigenetics

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“…2) [18][19][20][21][22][23]. Furthermore, when overexpressed on APC or when crosslinked as fusion proteins, DLL ligands promote T H 1 cell differentiation [18,20,22,[24][25][26].…”

Section: Induction Of T H 1-cell Differentiation By Notchmentioning

confidence: 99%

How are TH1 and TH2 effector cells made?

Amsen

Spilianakis²,

Flavell

2009

Current Opinion in Immunology

142

128

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SummaryDifferentiation of T H 1 and T H 2-effector cells proceeds through several phases: First, naïve CD4 + precursor cells are instructed to differentiate as appropriate to optimally fight the infectious threat encountered. This process is governed by the IL12 and IL4 cytokines, as well as by signaling through the Notch receptor. In response to these signals, transcription is initiated of lineage specific genes including the Ifnγ and Il4 genes as well as of genes encoding transcriptional regulators, such as Tbet and Gata3. The respective differentiation programs are reinforced by both positive and negative feedback mechanisms. Furthermore, epigenetic modifications of the lineage specific genes result in the emergence of regulatory elements, which control high level lineage restricted expression by both intra-and interchromosomal associations. Together, these mechanisms ensure stable inheritance of the differentiated fate in the numerous progeny of the original naïve CD4 + T cells.

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“…Specifically, it has been hypothesized that exposure to microbial products during early childhood may have an inhibitory effect on the development of allergic diseases [4][5][6]. Notably, in a series of well-performed epidemiological studies on children of European farmers (Allergy and Endotoxin), it was demonstrated that children who grew up in a farming environment and had close contact with farm animals exhibited significantly low levels of allergy and asthma in later life [7][8][9]. However, the proposed educating effect of exposure to various microbial products during early life on the development of immune regulatory function has not been tested in detail using experimental approaches.…”

Section: Introductionmentioning

confidence: 99%

Imprinted DC mediate the immune‐educating effect of early‐life microbial exposure

et al. 2009

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It has been long proposed that exposure to environmental factors early in life may have an educating effect on the development of immune regulatory functions. However, experimental studies on this issue are limited and the related molecular and cellular basis remains unclear. Here we report that neonatal exposure to killed bacteria (Chlamydia muridarum, originally called Chlamydia trachomatis mouse pneumonitis (MoPn)) changed the pattern of the hosts' immune responses to a model allergen (OVA) in adulthood. This was associated with altered phenotype and function of DC. We found that DC from adult mice treated neonatally with UV-killed MoPn exhibited distinct patterns of surface marker and TLR expression and cytokine production from control mice (DC from adult mice neonatally treated with vehicle, (Sham-DC)). More importantly, DC from adult mice treated neonatally with UV-killed MoPn induced significantly lower type-2 antigen-specific T-cell responses than Sham-DC shown in DC:T co-culture experiments in vitro and in adoptive transfer experiments in vivo. In addition, depletion of T cells in vivo largely abolished the phenotypic and functional alterations of DC caused by bacterial exposure, suggesting the involvement of T cell in this process. Our study demonstrates a central role of DC in linking the early-life exposure to microbial products and the balanced development of immune regulatory functions and the involvement of T cells in imprinting of the DC function.Key words: Allergy . DC . Hygiene hypothesis . IL-10 . TLR IntroductionThe immune system of a host experiences multiple influences from the outside world during development from birth to adult life. Numerous studies have demonstrated that environmental factors encountered during the developmental stage have considerable effect in shaping the pattern of immune responses in adult life. Therefore, the exposure to ''proper'' environmental antigens in early life might be important for the formation and maintenance of a balanced immune regulatory system in the host, thus preventing autoimmunity and allergic diseases [1,2].Over the past decades, the general burden of infections in the developed areas of the world has been reduced due to a better hygiene, and the ''hygiene hypothesis'' has been raised to explain the significant increase of allergic diseases [3,4]. Specifically, it has been hypothesized that exposure to microbial products during early childhood may have an inhibitory effect on the development of allergic diseases [4][5][6]. Notably, in a series of well-performed epidemiological studies on children of European farmers (Allergy and Endotoxin), it was demonstrated that children who grew up in a farming environment and had close contact with farm animals exhibited significantly low levels of allergy and asthma in later life [7][8][9]. However, the proposed educating effect of exposure to various microbial products during early life on the development of immune regulatory function has not been tested in detail using experimental approaches. 469More i...

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Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties

Cited by 250 publications

References 43 publications

Epigenotype switching at the CD14 and CD209 genes during differentiation of human monocytes to dendritic cells

Epigenotype switching at the CD14 and CD209 genes during differentiation of human monocytes to dendritic cells

How are TH1 and TH2 effector cells made?

Imprinted DC mediate the immune‐educating effect of early‐life microbial exposure

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