Volume 38, Issue 5, Pages (May 2013)

Slides:



Advertisements
Similar presentations
Volume 39, Issue 5, Pages (November 2013)
Advertisements

Volume 34, Issue 3, Pages (March 2011)
Volume 39, Issue 3, Pages (September 2013)
CLEC5A is critical for dengue virus–induced inflammasome activation in human macrophages by Ming-Fang Wu, Szu-Ting Chen, An-Hang Yang, Wan-Wan Lin, Yi-Ling.
Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection
Takashi Tanaka, Michelle A. Soriano, Michael J. Grusby  Immunity 
Volume 44, Issue 3, Pages (March 2016)
Volume 28, Issue 2, Pages (February 2008)
Volume 30, Issue 4, Pages (April 2009)
Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation  Timotheus Y.F. Halim, Ramona H.
Nod2-Induced Autocrine Interleukin-1 Alters Signaling by ERK and p38 to Differentially Regulate Secretion of Inflammatory Cytokines  Matija Hedl, Clara.
Volume 15, Issue 4, Pages (April 2014)
Volume 31, Issue 6, Pages (December 2009)
Volume 26, Issue 1, Pages (January 2007)
Volume 5, Issue 4, Pages (April 2009)
Volume 39, Issue 5, Pages (November 2013)
Volume 38, Issue 4, Pages (April 2013)
Volume 36, Issue 1, Pages (January 2012)
Timothy E. O’Sullivan, Lexus R. Johnson, Helen H. Kang, Joseph C. Sun 
The UPEC Pore-Forming Toxin α-Hemolysin Triggers Proteolysis of Host Proteins to Disrupt Cell Adhesion, Inflammatory, and Survival Pathways  Bijaya K.
Volume 47, Issue 5, Pages e6 (November 2017)
Integrin α5β1 Activates the NLRP3 Inflammasome by Direct Interaction with a Bacterial Surface Protein  Hye-Kyoung Jun, Sung-Hoon Lee, Hae-Ri Lee, Bong-Kyu.
Volume 29, Issue 2, Pages (August 2008)
Volume 42, Issue 5, Pages (May 2015)
Volume 31, Issue 1, Pages (July 2009)
Volume 141, Issue 5, Pages e2 (November 2011)
Volume 46, Issue 6, Pages e4 (June 2017)
Volume 29, Issue 4, Pages (October 2008)
Volume 26, Issue 5, Pages (May 2007)
Volume 37, Issue 4, Pages (October 2012)
Volume 47, Issue 4, Pages e3 (October 2017)
Estrogen receptor β agonist diarylpropionitrile inhibits lipopolysaccharide-induced regulated on activation normal T cell expressed and secreted (RANTES)
Heat Shock Transcription Factor 1 Is a Key Determinant of HCC Development by Regulating Hepatic Steatosis and Metabolic Syndrome  Xiongjie Jin, Demetrius.
Volume 12, Issue 1, Pages (July 2015)
Volume 38, Issue 6, Pages (June 2013)
Volume 33, Issue 2, Pages (August 2010)
Volume 36, Issue 2, Pages (February 2012)
Volume 33, Issue 3, Pages (September 2010)
Identifying Yersinia YopH-Targeted Signal Transduction Pathways that Impair Neutrophil Responses during In Vivo Murine Infection  Hortensia G. Rolán,
C5a Negatively Regulates Toll-like Receptor 4-Induced Immune Responses
Volume 22, Issue 2, Pages (February 2005)
Volume 41, Issue 4, Pages (October 2014)
Volume 33, Issue 6, Pages (December 2010)
Volume 14, Issue 2, Pages (August 2013)
Volume 32, Issue 5, Pages (May 2010)
Volume 44, Issue 3, Pages (March 2016)
Volume 32, Issue 4, Pages (April 2010)
Volume 27, Issue 3, Pages (September 2007)
Opposing Effects of TGF-β and IL-15 Cytokines Control the Number of Short-Lived Effector CD8+ T Cells  Shomyseh Sanjabi, Munir M. Mosaheb, Richard A.
Volume 36, Issue 4, Pages (April 2012)
Volume 35, Issue 2, Pages (August 2011)
Volume 19, Issue 3, Pages (September 2003)
Volume 30, Issue 6, Pages (June 2009)
Volume 8, Issue 4, Pages (October 2005)
Karima R.R. Siddiqui, Sophie Laffont, Fiona Powrie  Immunity 
Volume 34, Issue 5, Pages (May 2011)
Volume 32, Issue 2, Pages (February 2010)
Volume 40, Issue 4, Pages (April 2014)
Targeted Cleavage of Signaling Proteins by Caspase 3 Inhibits T Cell Receptor Signaling in Anergic T Cells  Irene Puga, Anjana Rao, Fernando Macian  Immunity 
Volume 28, Issue 5, Pages (May 2008)
Volume 35, Issue 4, Pages (October 2011)
Duy Pham, PhD, Sarita Sehra, PhD, Xin Sun, PhD, Mark H. Kaplan, PhD 
Volume 27, Issue 4, Pages (October 2007)
Volume 50, Issue 3, Pages e6 (March 2019)
Volume 31, Issue 6, Pages (December 2009)
CD14 Controls the LPS-Induced Endocytosis of Toll-like Receptor 4
Volume 24, Issue 1, Pages (January 2006)
Volume 46, Issue 2, Pages (April 2012)
Engagement of the Type I Interferon Receptor on Dendritic Cells Inhibits T Helper 17 Cell Development: Role of Intracellular Osteopontin  Mari L. Shinohara,
Volume 25, Issue 6, Pages (June 2017)
Presentation transcript:

Volume 38, Issue 5, Pages 1038-1049 (May 2013) The C-type Lectin Receptors Dectin-1, MR, and SIGNR3 Contribute Both Positively and Negatively to the Macrophage Response to Leishmania infantum  Lise Lefèvre, Geanncarlo Lugo-Villarino, Etienne Meunier, Alexis Valentin, David Olagnier, Hélène Authier, Carine Duval, Christophe Dardenne, José Bernad, Jean Loup Lemesre, Johan Auwerx, Olivier Neyrolles, Bernard Pipy, Agnès Coste  Immunity  Volume 38, Issue 5, Pages 1038-1049 (May 2013) DOI: 10.1016/j.immuni.2013.04.010 Copyright © 2013 Elsevier Inc. Terms and Conditions

Immunity 2013 38, 1038-1049DOI: (10.1016/j.immuni.2013.04.010) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 M2b-like Macrophages Express Dectin-1, MR, and SIGNR3 during L.i. Infection in B6 Genetic Background (A, C, and E) qRT-PCR analysis of biological markers for M1 and M2 polarization programs in peritoneal macrophages from B6 mice in response to L.i. stimulation. (B and D) Cell-surface protein levels for the indicated polarization markers as quantified by flow cytometry after challenge with L.i. (F) Protein levels for the indicated genes as quantified by ELISA in the supernatant of peritoneal macrophages from B6 mice in response to L.i. stimulation. For qRT-PCR analysis, ELISA quantification, and flow cytometry geomean, infection with L.i. is denoted by black bars (+L.i.) and the mock control by white bars (−L.i.). For flow cytometry overlay profiles, macrophages challenged with L.i. are denoted by unfilled black overlay (+L.i.) and the mock control by filled gray overlay (−L.i.) and geomean fluorescence values were noted. Results correspond to mean ± SEM of triplicates. Data are representative of three independent experiments. *p < 0.05, **p < 0.001 compared to the mock control (−L.i.). The mRNA levels were represented in fold induction relative to the mRNA levels observed for the mock control samples. See also Figure S1 and Table S2. Immunity 2013 38, 1038-1049DOI: (10.1016/j.immuni.2013.04.010) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 2 Dectin-1, MR, and SIGNR3 Have Distinct Contributions to the L.i. Infection Outcome and the Functional Macrophage Response (A–C) Clec7a−/−, Mrc1−/−, and Cd209d −/− mouse models (black) and their corresponding WT counterparts (gray, +/+), were infected (i.p.) with 50 × 106 L.i. for 14 days. The number of mice is listed in (B). For the adoptive transfer experiment (C), each CLR-deficient mouse was injected i.p. with 6 × 106 macrophages harvested from their respective WT counterpart 10 hr before L.i. inoculation (AT) (n = 6 mice per group). Quantification of L.i. parasite number in the spleen (A, C) or in the blood (B, C) for each CLR-deficient mouse model was measured by qRT-PCR analysis. The number of mice that tested positive for L.i. in the blood after 2 weeks of infection was determined by qRT-PCR analysis (B). Data are represented as mean ± SEM; *p < 0.05 compared to WT mice. (D–F) Proliferation (D), binding and phagocytosis (E), and ROS induction (F) of L.i.-luciferase were measured in peritoneal macrophages from each CLR-deficient mouse model, compared to its corresponding WT (+/+) counterpart. For indicated measurements, pretreatment with Bay was performed before the challenge with L.i. Data are expressed as fold induction relative to the luminescence or chemiluminescence observed for WT without treatment. Results correspond to mean ± SEM of triplicates and are representative of at least three independent experiments. *p < 0.05, **p < 0.001 compared to untreated WT and #p < 0.05, ##p < 0.001 compared to untreated CLR-deleted mice. See also Figure S2. Immunity 2013 38, 1038-1049DOI: (10.1016/j.immuni.2013.04.010) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 3 Dectin-1-Syk-p47phox and MR-AA-NADPH Oxidase Signaling Pathways Induce the Respiratory Burst in Response to Leishmania (A) Phosphorylated p47phox immunoblot after L.i. infection (3 hr) in peritoneal macrophages from each CLR-deficient mouse model (−/−) and its corresponding WT counterpart (+/+). “C” denotes nontreated control samples. Pretreatment with Bay was performed before the challenge with L.i. Band intensity was quantified with Image J software and was represented as the ratio between the band intensities of phosphorylated p47phox and of p47phox. (B and C) AA release (B) and ROS production (C) by peritoneal macrophages from B6 mice treated or not with MAFP in response to L.i. challenge. Data are expressed as fold induction relative to untreated macrophages. (D) AA release was measured for peritoneal macrophages from each CLR-deficient mouse model in response to L.i. challenge and expressed as the percentage of AA released relative to that of WT (+/+) macrophages (set arbitrarily at 0%). Results correspond to mean ± SEM of triplicates and are representative of three independent experiments. *p < 0.05, **p < 0.001 compared to untreated WT. Immunity 2013 38, 1038-1049DOI: (10.1016/j.immuni.2013.04.010) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 4 The Inflammatory Cytokine Induction in Response to L.i. Is Controlled Differently by CLRs (A and B) IL-1β protein (A) and mRNA (B) levels in peritoneal macrophages from each CLR-deficient mouse model (black bar) and its corresponding WT counterpart (gray bar, +/+) after L.i. challenge and measured by ELISA and qRT-PCR, respectively. (C) Inhibition of IL-1β release by peritoneal macrophage from each CLR-deficient mouse model (black bar, −/−) and its appropriate WT counterpart (gray bar), pretreated with Z-VAD-FMK (Zvad) and challenged with L.i., and quantified by ELISA. Results are expressed as the percentage of inhibition of IL-1β secretion relative to the corresponding untreated control but challenged with L.i. (D) Immunoblot blot analysis of caspase-1 p20 fragment cleavage in peritoneal macrophages from each CLR-deficient mouse model (−/−) and its corresponding WT counterpart (+/+) challenged with L.i. (+L.i.). “C” indicates uninfected control sample. Band intensity was quantified with Image J software and was represented as the ratio between the band intensities of p20 and of β-actin. (E) Inhibition of IL-1β release by peritoneal macrophages from each CLR-deficient mouse model (black bar, −/−) and its corresponding WT counterpart (gray bar, +/+), pretreated with either Latrunculin A, Bay, or N-acetyl-cysteine, and then challenged with L.i. and quantified by ELISA. Results are expressed as the percentage of IL-1β secretion inhibition relative to the corresponding untreated control but challenged with L.i. (F) LTB4 production by peritoneal macrophages from each CLR-deficient mouse model (black bar, −/−) and its corresponding WT counterpart (gray bar, +/+), then challenged with L.i. and quantified by enzyme immunoassay (EIA). See also Figure S3. (G) qRT-PCR analysis of Lta4h, Alox5, and Alox15 mRNA levels in peritoneal macrophages from each CLR-deficient mouse model (black bar, −/−) and its corresponding WT counterpart (gray bar, +/+) in response to L.i. challenge. The mRNA levels were represented in fold induction relative to the mRNA level observed for the corresponding WT sample infected with L.i. (H) IL-1β release by peritoneal macrophages from Cd209d-deficient mice (black bar, −/−) and its corresponding WT counterpart (gray bar, +/+), pretreated or not with the FLAP inhibitor MK886, in the presence or absence of LTB4 cotreatment, challenged with L.i., and then measured by ELISA. Data are shown as mean ± SEM of triplicates and are representative of at least three independent experiments. *p < 0.05, **p < 0.001 compared to untreated WT and #p < 0.05, ##p < 0.001 compared to untreated CLR-deficient mice (A–C, E) or compared to CLR-deficient mice treated only with MK886 (H). Immunity 2013 38, 1038-1049DOI: (10.1016/j.immuni.2013.04.010) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 5 Dectin-1, MR, and DC-SIGN Contribute to the Modulation of Parasite Proliferation in Human Monocyte-Derived Macrophages (A) CLR silencing in human macrophages. Genes encoding for the indicated CLRs were silenced with the lipid-based forward transfection of specific SMARTpools (target) and nontargeting (control) siRNAs in adherent MDMs, as described in the Experimental Procedures section. Silencing was then confirmed by flow cytometry analysis. Data were displayed as the median of fluorescence difference. *p < 0.05, **p < 0.003 of siRNA target compared to siRNA control. (B–D) Luciferase activity indicating proliferation (B) and ROS production (C), or IL-1β release (D), in MDMs transfected with siRNAs targeting either each of the indicated genes or nontargeting (control), and challenged with L.i. (black) or not (white). (E) LTB4 production by MDMs transfected with the indicated siRNAs, challenged with L.i., and quantified by EIA. (F) IL-1β release in MDMs transfected simultaneously with the indicated siRNAs, challenged with L.i., and quantified by ELISA. Data are shown as mean ± SEM of triplicates and are representative of three independent experiments. *p < 0.05, **p < 0.001 compared to siRNA control (B, D–F) or *p < 0.05, **p < 0.001 of infected cells (black) compared to that noninfected (white) (C) and #p < 0.05 compared to siRNA CD209 (F). See also Figure S4 and Tables S1 and S2. Immunity 2013 38, 1038-1049DOI: (10.1016/j.immuni.2013.04.010) Copyright © 2013 Elsevier Inc. Terms and Conditions