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Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation  Kathrin Straubinger,

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Presentation on theme: "Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation  Kathrin Straubinger,"— Presentation transcript:

1 Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation  Kathrin Straubinger, PhD, Sabine Paul, VTA, Olivia Prazeres da Costa, MSc, Manuel Ritter, PhD, Thorsten Buch, PhD, Dirk H. Busch, MD, Laura E. Layland, PhD, Clarissa U. Prazeres da Costa, MD  Journal of Allergy and Clinical Immunology  Volume 134, Issue 6, Pages e10 (December 2014) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Pregnancy during the TH1 or Reg phases, but not the TH2 phase, of schistosomiasis leads to reduced AAI. Total leukocytes in BAL (Fig 1, A-C), total eosinophils in BAL (Fig 1, D-F), lung inflammation (Fig 1, G-I), and representative PAS-stained lung tissue sections (Fig 1, J-M) are shown. For each immune phase, OVA-treated offspring (n = 5-19) and PBS-treated offspring (n = 3-7) from infected (n ≥ 2) and uninfected mothers (n ≥ 3) are indicated. Data are shown as mean ± SEM and represent 1 of 2 independent experiments per immune phase. Asterisks show statistical differences between OVA-treated groups (*P < .05; **P < .01). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Protection against AAI in TH1 phase derived offspring is not transferred via the germline. The outcome of AAI was compared in the OVA-treated (n = 6-10) and PBS-treated (n = 3) offspring stemming from embryos of uninfected mothers (n = 6) or TH1 phase–infected mothers (n = 10). Total leukocytes in BAL (Fig 2, A), total eosinophils in BAL (Fig 2, B), lung inflammation (Fig 2, C), and goblet cells (Fig 2, D) are shown. Data is shown as mean ± SEM and represents 1 experiment. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Maternal schistosomiasis alters gene expression and schistosome-specific responses in placental cells. Heatmap (Fig 3, A) depicting significantly down-regulated (blue) and up-regulated (yellow) genes from day 18 placentas (n ≥ 5 per group) from infected vs uninfected mothers. Venn diagram shows number of overlapping differentially expressed genes between the 3 phases. Relative expression of target gene mRNA normalized to hypoxanthine-guanine phosphoribosyltransferase (HPRT) (Fig 3, B) from day 18 placentas (n = 4-5 per group) of infected compared with uninfected mothers. Cytokine production (Fig 3, C) from SEA-restimulated day 18 placental cells from uninfected compared with infected (n = 3-4 per group) mothers. Quantification of CD45+CD4+ cytokine producing cells (Fig 3, D) from pooled placentas (n ≥ 26 per group) by ICS. Results are shown as mean ± SEM. (∗P < .05; ∗∗P < .01.) Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Parameters of AAI are aggravated in offspring from IFN-γ-knockout mothers mated in the acute phase of schistosomiasis. Total leukocytes in BAL (Fig 4, A), eosinophils in BAL (Fig 4, B), lung inflammation (Fig 4, C), representative PAS-stained lung sections (Fig 4, D-F), and goblet cells (Fig 4, G) are shown. OVA-treated IFN-γ+/+ (n = 8) and IFN-γ+/− offspring (n = 4) from uninfected mothers; OVA-treated IFN-γ+/− offspring (n = 12) from infected mothers (n ≥ 2). Data shows mean ± SEM from 1 of 2 studies. Asterisks show statistical differences (*P < .05; **P < .01). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E1 Protocol for OVA-induced AAI in offspring from uninfected and TH1, TH2, and Reg phase S mansoni–infected mothers. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E2 Immune phases during schistosome infection influence fetal weight. IL-5, IL-4, IL-10 and IFN-γ production (Fig E2, A) in SEA-restimulated splenocytes from S mansoni–infected mice at weeks 5 (n = 4), 10 (n = 4), 12 (n = 4), 16 (n = 4), and 29 (n = 4) post-infection. Weight of fetuses (Fig E2, B) from litters with 7 to 10 offspring at day 18 of pregnancy. Weight (Fig E2, C) of 9-week-old male (m) and female (f) offspring. Offspring from uninfected mothers (n = 38-46), mothers mated at week 3.5 (n = 14-19), week 11 (n = 28-46), and week 16 (n = 23-24) post-infection. Data are shown as mean ± SEM. Asterisks show statistical differences (**P < .01; ***P < .001). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E3 BAL cell differentiation and goblet cell numbers of offspring from uninfected and infected mothers. Numbers of macrophages (Mac.), lymphocytes (Lymph.), and neutrophils (Neut.) in BAL and goblet cells in lung sections after AAI in TH1 phase (Fig E3, A and D), TH2 phase (Fig E3, B and E) and Reg phase (Fig E3, C and F) offspring. For each immune phase, OVA-treated offspring (n = 5-19) and PBS-treated offspring (n = 3-7) from infected (n ≥ 2) and uninfected mothers (n ≥ 3). Data is shown as mean ± SEM and represents 1 out of 2 independent experiments per immune phase. Asterisks show statistical differences between OVA-treated groups (*P < .05; **P < .01). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E4 Offspring from TH1 or Reg phase–infected mothers present dampened OVA-specific immune responses. OVA-specific serum IgE (Fig E4, A-C), IL-5 production in OVA restimulated splenocytes (Fig E4, D-F) and IL-10 responses in OVA restimulated splenocytes (Fig E4, G-I) are shown. For each immune phase, OVA-treated offspring (n = 5-19) and PBS-treated offspring (n = 3-7) from infected (n ≥ 2) and uninfected mothers (n ≥ 3). Data is shown as mean ± SEM and represents 1 of 2 independent experiments per immune phase. Asterisks show statistical differences between OVA-treated groups (*P < .05; **P < .01). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E5 BAL cell differentiation, OVA-specific IgE and lung sections in offspring from embryos of uninfected mothers or TH1 phase infected mothers. Numbers of macrophages (Mac.), lymphocytes (Lymph.), and neutrophils (Neut.) in BAL (Fig E5, A). OVA-specific serum IgE (Fig E5, B). Representative PAS-stained lung sections (Fig E5, C and D). OVA-treated (n = 6-10) and PBS-treated (n = 3) offspring from embryos of uninfected mothers (n = 6) or TH1 phase infected mothers (n = 10). Data is shown as mean ± SEM and represents 1 experiment. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Fig E6 IFN-γ detection in placentas from TH1 phase infected mice. CTHPRT/CTIFN-g values obtained by RT-PCR from placental RNA at day 12 to 13 of pregnancy (n = 3-5 per group). CT, Cycle threshold. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Fig E7 Parameters of AAI are aggravated in offspring from IFN-γ knockout mothers mated in the acute phase of schistosomiasis. Comparison of SEA-specific cytokines (Fig E7, A) from splenocytes of wild-type (WT) and IFN-γ−/− (n = 3-5 per group per time point). Macrophages (Mac.), lymphocytes (Lymph.), and neutrophils (Neut.) in BAL (Fig E7, B). OVA-specific IL-5 in splenocytes (Fig E7, C). OVA-specific serum IgE (Fig E7, D). OVA-treated IFN-γ+/+ (n = 8) and IFN-γ+/− offspring (n = 4) from uninfected mothers; OVA-treated IFN-γ+/− offspring (n = 12) from infected mothers (n ≥ 2). Data shows mean ± SEM from 1 of 2 studies. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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