What’s Wrong in What’s Wrong in Atopy & Allergy? Atopy & Allergy? Schweizerisches Institut für Allergie- und Asthmaforschung, Davos PD Dr Liam O‘Mahony PD Dr Liam O‘Mahony Swiss Insititute of Allergy and Asthma Research Swiss Insititute of Allergy and Asthma Research University of Zürich, Davos, Switzerland University of Zürich, Davos, Switzerland 4 4 th th December 2015 December 2015
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What’s Wrong in Atopy & Allergy? Schweizerisches Institut für Allergie- und Asthmaforschung, Davos PD Dr Liam O‘Mahony Swiss Insititute of Allergy and.
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What’s Wrong in What’s Wrong in Atopy & Allergy?Atopy & Allergy?
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
PD Dr Liam O‘MahonyPD Dr Liam O‘MahonySwiss Insititute of Allergy and Asthma ResearchSwiss Insititute of Allergy and Asthma Research
University of Zürich, Davos, SwitzerlandUniversity of Zürich, Davos, Switzerland44thth December 2015 December 2015
Atopy and AllergySchweizerisches Institut für Allergie- und Asthmaforschung, Davos
“Atopy” is characterized by a tendency to be hyperallergic, also refers to a genetically mediated predisposition to an excessive IgE reaction
“Allergy” - a damaging immune response by the body to a substance, especially a particular food, pollen, fur, or dust, to which it has become hypersensitive
“Hypersensitivity” – lack of immunological regulation
Allergic reactions are designed to eliminate a “threat”
Bacterial Stimulation of Regulatory CellsSchweizerisches Institut für Allergie- und Asthmaforschung, Davos
Ngoi et al., Discov Med 2011
• Alternative defense strategy that minimizes the impact of an invader on host fitness• Allows for the establishment of a robust microbiome, which can provide nutrients and added protection to the host
Mucosal lymphoid structures poorly developedLamina propria cellularity significantly reducedInnate immune system under-developed (e.g. phagocytic activity)B cell antibody response (particularly IgA & IgE) is significantly differentTh2 dominant responses, diminished Treg and Th17 responsesHowever, overall numbers of T cell & NK lymphoid populations are comparable to conventionally colonised animals
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
Germ Free Animals
Olszak et al., Science 2012
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
Colonisation Timing is Important
Lyons et al., CEA 2010
Bifidobacteria Bifidobacteria
*
*p<0.05
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
Induction of Tregs in Germ Free Animals
0
100
200
300
OVA
-Spe
cific
IgE
ng/m
l
Negative Control
Placebo Bifidobacterium AH1205
Bifidobacterium AH1206
Lactobacillus AH102
OVA + Cholera Toxin
Lyons et al., CEA 2010
*
*p<0.05
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
IgE Response Inhibited by Treg Promoting Bacteria
Noval Rivas et al., J Allergy Clin Immunol 2013
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
Pro- Allergic Microbiome is Transferable
IL-12TNF-
IL-10TGFIDORALDH2
Regulatory T Cells
IL-10IDOP
MTLR-2/6
CLR/DC-SIGN
TLR-9
Bifidobacterium
Intestinal Epithelial Cells
Schweizerisches Institut für Allergie- und Asthmaforschung, Davos
Bacterial-Dendritic Cell-Lymphocyte Regulation
O‘Hara et al., Immunology 2006O‘Mahony et al., AJPGLP 2006Sibartie et al., BMC Immunol 2009Konieczna et al., Gut 2012Konieczna et al., Gut Microbes 2012Symonds et al., Clin Transl Gastro 2012Scully et al., Cell Immunol. 2013Konieczna et al., PLoS One 2013