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Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury

Nature Medicine volume 5, pages 392–398 (1999)Cite this article

Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause fatal acute lung infections in critically ill individuals. Damage to the lung epithelium is associated with the expression of toxins that are directly injected into eukaryotic cells through a type III-mediated secretion and translocation mechanism. Here we show that the P. aeruginosa homolog of the Yersinia V antigen, PcrV, is involved in the translocation of type III toxins. Vaccination against PcrV ensured the survival of challenged mice and decreased lung inflammation and injury. Antibodies to PcrV inhibited the translocation of type III toxins.

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Figure 1: Phenotypic analysis of PA103ΔpcrV.
Figure 2: PcrV mediates ExoY translocation into J774 cells and anti-PcrV IgG inhibits ExoY translocation.
Figure 3: The effect of active immunization, passive immunization and co-instillation of immune IgG on survival and lung injury.
Figure 4: Anti-PcrV IgG prevents macrophage killing and preserves phagocytic function.
Figure 5: Anti-PcrV IgG reduces bacterial burden and enhances macrophage survival in vivo.
Figure 6: Co-instillation of anti-PcrV IgG reduces the inflammatory response.

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Acknowledgements

The technical assistance from R. Shanks and A.J. Vallis is appreciated. V Finck-Barbançon contributed LPS-free rExoU for these studies. This work was supported by Public Service Grants from the National Institute of Allergy and Infectious Diseases, the National Heart, Lung Blood Institute, and the Cystic Fibrosis Foundation.

Author information

Author notes

  1. Teiji Sawa and Timothy L. Yahr: T.S. & T.L.Y. contributed equally to this study.

Authors and Affiliations

  1. Department of Anesthesia and Perioperative Care, The University of California, San Francisco, 513 Parnassus, S-261 , San Francisco, 94143-0542, California, USA

    Teiji Sawa, Maria Ohara, Kiyoyasu Kurahashi, Michael A. Gropper & Jeanine P. Wiener-Kronish

  2. Department of Physiology, The University of California San Francisco, 513 Parnassus, S-261, San Francisco , 94143-0542, California, USA

    Michael A. Gropper

  3. Department of Medicine, The University of California San Francisco, 513 Parnassus, S-261, San Francisco , 94143-0542, California, USA

    Jeanine P. Wiener-Kronish

  4. Cardiovascular Research Institute, The University of California, San Francisco, 513 Parnassus, S-261, San Francisco, 94143-0542, California, USA

    Jeanine P. Wiener-Kronish

  5. Department of Biochemistry, Dartmouth Medical School, Hanover, 03755, New Hampshire, USA

    Timothy L. Yahr

  6. Department of Microbiology and Molecular Genetics Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, 53226, Wisconsin, USA

    Dara W. Frank

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  1. Teiji Sawa
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Correspondence to Dara W. Frank.

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Sawa, T., Yahr, T., Ohara, M. et al. Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat Med 5, 392–398 (1999). https://doi.org/10.1038/7391

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