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Yersinia pestis Can Reside in Autophagosomes and Avoid Xenophagy in Murine Macrophages by Preventing Vacuole Acidification

Pujol, Céline ; Klein, Kathryn A ; Romanov, Galina A ; Palmer, Lance E ; Cirota, Carol ; Zhao, Zijiang ; Bliska, James B

Infection and Immunity, 2009-06, Vol.77 (6), p.2251-2261 [Revista revisada por pares]

Washington, DC: American Society for Microbiology

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Yersinia pestis Can Reside in Autophagosomes and Avoid Xenophagy in Murine Macrophages by Preventing Vacuole Acidification
Autor: Pujol, Céline ; Klein, Kathryn A ; Romanov, Galina A ; Palmer, Lance E ; Cirota, Carol ; Zhao, Zijiang ; Bliska, James B
Materias: Acidification ; Animals ; Bacteriology ; Biological and medical sciences ; Biomarkers - analysis ; Cell activation ; Cell survival ; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions ; Colony Count, Microbial ; Electron microscopy ; endosomes ; Fundamental and applied biological sciences. Psychology ; g-Interferon ; Green fluorescent protein ; Hydrogen-Ion Concentration ; imaging ; Immunoblotting ; Lysosomes ; Macrophages ; Macrophages - microbiology ; Mice ; Mice, Inbred C57BL ; Microbial Viability ; Microbiology ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; Miscellaneous ; Pathogens ; pH effects ; Phagocytosis ; Phagosomes ; Phagosomes - chemistry ; Phagosomes - microbiology ; Phagosomes - ultrastructure ; Replication ; Vacuoles ; Yersinia pestis ; Yersinia pestis - immunology ; Yersinia pestis - physiology
Es parte de: Infection and Immunity, 2009-06, Vol.77 (6), p.2251-2261
Notas: ObjectType-Article-2
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C.P. and K.A.K. contributed equally to this work.
Present address: UR1282, Infectiologie Animale, Santé Publique (IASP-311), INRA Centre de Tours, F-37380 Nouzilly, France.
Present address: Siemens Corporate Research, 755 College Rd. East, Princeton, NJ 08540.
Corresponding author. Mailing address: Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794-5120. Phone: (631) 632-8782. Fax: (631) 632-4294. E-mail: jbliska@ms.cc.sunysb.edu
Editor: A. J. Bäumler
Descripción: Yersinia pestis survives and replicates in phagosomes of murine macrophages. Previous studies demonstrated that Y. pestis-containing vacuoles (YCVs) acquire markers of late endosomes or lysosomes in naïve macrophages and that this bacterium can survive in macrophages activated with the cytokine gamma interferon. An autophagic process known as xenophagy, which destroys pathogens in acidic autophagolysosomes, can occur in naïve macrophages and is upregulated in activated macrophages. Studies were undertaken here to investigate the mechanism of Y. pestis survival in phagosomes of naïve and activated macrophages and to determine if the pathogen avoids or co-opts autophagy. Colocalization of the YCV with markers of autophagosomes or acidic lysosomes and the pH of the YCV were determined by microscopic imaging of infected macrophages. Some YCVs contained double membranes characteristic of autophagosomes, as determined by electron microscopy. Fluorescence microscopy showed that ~40% of YCVs colocalized with green fluorescent protein (GFP)-LC3, a marker of autophagic membranes, and that YCVs failed to acidify below pH 7 in naïve macrophages. Replication of Y. pestis in naïve macrophages caused accumulation of LC3-II, as determined by immunoblotting. While activation of infected macrophages increased LC3-II accumulation, it decreased the percentage of GFP-LC3-positive YCVs (~30%). A viable count assay showed that Y. pestis survived equally well in macrophages proficient for autophagy and macrophages rendered deficient for this process by Cre-mediated deletion of ATG5, revealing that this pathogen does not require autophagy for intracellular replication. We conclude that although YCVs can acquire an autophagic membrane and accumulate LC3-II, the pathogen avoids xenophagy by preventing vacuole acidification.
Editor: Washington, DC: American Society for Microbiology
Idioma: Inglés

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Yersinia pestis Can Reside in Autophagosomes and Avoid Xenophagy in Murine Macrophages by Preventing Vacuole Acidification

Pujol, Céline ; Klein, Kathryn A ; Romanov, Galina A ; Palmer, Lance E ; Cirota, Carol ; Zhao, Zijiang ; Bliska, James B

Washington, DC: American Society for Microbiology

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