Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation Nanna Fyhrquist, PhD, Lasse Ruokolainen, PhD, Alina.

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Presentation transcript:

Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation Nanna Fyhrquist, PhD, Lasse Ruokolainen, PhD, Alina Suomalainen, BSc, Sari Lehtimäki, PhD, Ville Veckman, PhD, Johanna Vendelin, PhD, Piia Karisola, PhD, Maili Lehto, PhD, Terhi Savinko, PhD, Hanna Jarva, MD, Timo U. Kosunen, MD, Jukka Corander, PhD, Petri Auvinen, PhD, Lars Paulin, PhD, Leena von Hertzen, PhD, Tiina Laatikainen, PhD, Mika Mäkelä, MD, Tari Haahtela, MD, Dario Greco, PhD, Ilkka Hanski, PhD, Harri Alenius, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 6, Pages 1301-1309.e11 (December 2014) DOI: 10.1016/j.jaci.2014.07.059 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Network analysis of the relative abundance of skin microbial genera and PBMC gene expression in healthy (A) and atopic (B) subjects. Th1, T helper type 1 (blue); Th2, T helper type 2 (red); Th17, T helper type 17 (yellow); Treg, T regulatory/immunoregulatory (green) genes. Red and blue edges indicate positive and negative correlations, respectively, and the color hue indicates the strength of the correlation. Sample size is 46 healthy and 28 atopic subjects. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 The expression of IL10 RNA (***P = .0004) and IL-10 protein (P = .079; A) and FOXP3 RNA (**P = .004; B, left panel) in 24-hour unstimulated PBMC cultures and TGFB RNA (**P = .0053; B, right panel) in 6-hour Bet v 1–stimulated PBMC cultures correlated with the relative abundance of Acinetobacter species on the skin in healthy (open symbols) but not atopic (solid symbols) subjects. Sample size is 46 healthy and 28 atopic subjects. RQ, Relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 A, TH2-type responses correlated (*P = .021) with TH1/Treg cell–type responses in the healthy (open symbols) but not atopic (solid symbols) subjects. B and C, In the healthy subjects IFNG expression correlated with IL13 expression (***P = .0005) and was at a relatively higher level (**P < .01; Fig 3, B), and IL4 expression correlated with TGFB expression (**P = .0002; Fig 3, C). Sample size is 46 healthy and 28 atopic subjects. RQ, Relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Heat-inactivated Acinetobacter lwoffii (Al) induced the expression of IL12 (A) and IL10, Delta-like-4, and IL27 (B) in human moDCs and TNF and IL10, but not TSLP (C), in human primary keratinocytes. Sa, Staphylococcus aureus; Se, Staphylococcus epidermidis. *P < .05 and **P < .01. Bars represent means ± SEMs (n = 3-5 per group). Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Intradermal injections of A lwoffii (Al; A) reduced lung inflammation (B), eosinophil counts in bronchoalveolar lavage fluid and TH2 cytokine expression in lung tissue (C), and OVA-specific IgE and IgG2a levels in serum (D). E, A lwoffii induced IL-10 and IFN-γ in the skin. S epidermidis (Se) was used as a control. *P < .05, **P < .01, and ***P < .001. Bars represent means ± SEMs (n = 8 per group). i.d., Intradermal; i.n., intranasal; RQ, relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Expression of IL10 at the protein level corresponds closely to the level of RNA transcription in PBMCs in healthy (left panel) and atopic (right panel) subjects. Sample size is 46 healthy and 28 atopic subjects. RQ, Relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Expression of AHR in PBMCs correlates with the abundance of Acinetobacter species on the skin of healthy (green circles) but not atopic (violet squares) subjects. Sample size is 46 healthy and 28 atopic subjects. RQ, Relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 A, The original PBMC population consisted of 56% CD3+ T lymphocytes (middle panel) and 12.6% CD14+ monocytes (right panel). FSC, Forward scatter; SSC, side scatter. B and C, After cell separation, CD3+ cells were 98% pure (Fig E3, B), and the CD14+ cell subset was 97% pure (Fig E3, C; isotype control is shown at right). D, The relative expression of cytokines was extrapolated based on the fraction of each cell type in donors' PBMCs. Bars represent mean ± SEM (n = 3 per group). RQ, Relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Linear regression plots of gene expression levels of IL-13 versus IFN-γ (6-hour unstimulated PBMCs; A), IL-13 versus IL-27 (6-hour Bet v 1–stimulated PBMCs; B), IL-13 versus IL-27 (6-hour Phl p 1–stimulated PBMCs; C), IL-4 versus IL-27 (6-hour Bet v 1–stimulated PBMCs; D), IL-4 versus Foxp3 (6-hour unstimulated PBMCs; E), and IL-4 versus IL-10 (24-hour unstimulated PBMCs; F). Green open symbols, Healthy; violet solid symbols, atopic. Sample size is 46 healthy and 28 atopic subjects. RQ, Relative quantity. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Representative images of immune cells in bronchoalveolar lavage fluid cytospin preparations in control (A) and OVA-sensitized (B) mice and in OVA-sensitized mice that were treated intradermally with A lwoffii (C) or S epidermidis (D). Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 The production of IL-10 protein by anti-human CD3– and anti-human CD28–stimulated PBMCs correlates (P = .031) with the relative abundance of Acinetobacter species on the skin in healthy (green open symbols) but not atopic (violet solid symbols) subjects. Sample size is 46 healthy and 28 atopic subjects. Journal of Allergy and Clinical Immunology 2014 134, 1301-1309.e11DOI: (10.1016/j.jaci.2014.07.059) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions