Pierre Louis Goossens

Publications (4)19.8 Total impact

• Article: Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.

  Fabien Dumetz, Grégory Jouvion, Huot Khun, Ian Justin Glomski, Jean-Philippe Corre, Clémence Rougeaux, Wei-Jen Tang, Michèle Mock, Michel Huerre, Pierre Louis Goossens
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  ABSTRACT: Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection.
  American Journal Of Pathology 06/2011; 178(6):2523-35. · 4.89 Impact Factor
• Source

  Available from: Ronan Le Goffic

  Article: Edema toxin impairs anthracidal phospholipase A2 expression by alveolar macrophages.

  Benoit Raymond, Dominique Leduc, Lucas Ravaux, Ronan Le Goffic, Thomas Candela, Michel Raymondjean, Pierre Louis Goossens, Lhousseine Touqui
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  ABSTRACT: Bacillus anthracis, the etiological agent of anthrax, is a spore-forming gram-positive bacterium. Infection with this pathogen results in multisystem dysfunction and death. The pathogenicity of B. anthracis is due to the production of virulence factors, including edema toxin (ET). Recently, we established the protective role of type-IIA secreted phospholipase A2 (sPLA2-IIA) against B. anthracis. A component of innate immunity produced by alveolar macrophages (AMs), sPLA2-IIA is found in human and animal bronchoalveolar lavages at sufficient levels to kill B. anthracis. However, pulmonary anthrax is almost always fatal, suggesting the potential impairment of sPLA2-IIA synthesis and/or action by B. anthracis factors. We investigated the effect of purified ET and ET-deficient B. anthracis strains on sPLA2-IIA expression in primary guinea pig AMs. We report that ET inhibits sPLA2-IIA expression in AMs at the transcriptional level via a cAMP/protein kinase A-dependent process. Moreover, we show that live B. anthracis strains expressing functional ET inhibit sPLA2-IIA expression, whereas ET-deficient strains induced this expression. This stimulatory effect, mediated partly by the cell wall peptidoglycan, can be counterbalanced by ET. We conclude that B. anthracis down-regulates sPLA2-IIA expression in AMs through a process involving ET. Our study, therefore, describes a new molecular mechanism implemented by B. anthracis to escape innate host defense. These pioneering data will provide new molecular targets for future intervention against this deadly pathogen.
  PLoS Pathogens 01/2008; 3(12):e187. · 9.13 Impact Factor
• Chapter: Spore Surface Components and Protective Immunity to Bacillus anthracis

  Patricia Sylvestre, Ian Justin Glomski, Evelyne Couture-Tosi, Pierre Louis Goossens, Michèle Mock
  12/2007: pages 19-23;
• Article: Cutting Edge: IFN-gamma-producing CD4 T lymphocytes mediate spore-induced immunity to capsulated Bacillus anthracis.

  Ian Justin Glomski, Jean-Philippe Corre, Michèle Mock, Pierre Louis Goossens
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  ABSTRACT: Virulent strains of Bacillus anthracis produce immunomodulating toxins and an antiphagocytic capsule. The toxin component-protective Ag is a key target of the antianthrax immune response that induces production of toxin-neutralizing Abs. Coimmunization with spores enhances the antitoxin vaccine, and inactivated spores alone confer measurable protection. We aimed to identify the mechanisms of protection induced in inactivated-spore immunized mice that function independently of the toxin/antitoxin vaccine system. This goal was addressed with humoral and CD4 T lymphocyte transfer, in vivo depletion of CD4 T lymphocytes and IFN-gamma, and Ab-deficient (muMT(-/-)) or IFN-gamma-insensitive (IFN-gammaR(-/-)) mice. We found that humoral immunity did not protect from nontoxinogenic capsulated bacteria, whereas a cellular immune response by IFN-gamma-producing CD4 T lymphocytes protected mice. These results are the first evidence of protective cellular immunity against capsulated B. anthracis and suggest that future antianthrax vaccines should strive to augment cellular adaptive immunity.
  The Journal of Immunology 04/2007; 178(5):2646-50. · 5.79 Impact Factor