Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection.
The mucosal epithelium consists of polarized cells with distinct apical and basolateral membranes that serve as functional and physical barriers to external pathogens. The apical surface of the epithelium constitutes the first point of contact between mucosal pathogens, such as Pseudomonas aeruginosa, and their host. We observed that binding of P. aeruginosa aggregates to the apical surface of polarized cells led to the striking formation of an actin-rich membrane protrusion with inverted polarity, containing basolateral lipids and membrane components. Such protrusions were associated with a spatially localized host immune response to P. aeruginosa aggregates that required bacterial flagella and a type III secretion system apparatus. Host protrusions formed de novo underneath bacterial aggregates and involved the apical recruitment of a Par3/Par6α/aPKC/Rac1 signaling module for a robust, spatially localized host NF-κB response. Our data reveal a role for spatiotemporal epithelial polarity changes in the activation of innate immune responses.
Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Cindy S
CS
Tran
Division of Infectious Disease, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Yoni
Y
Eran
Division of Infectious Disease, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Travis R
TR
Ruch
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
David M
DM
Bryant
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Anirban
A
Datta
Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Paul
P
Brakeman
Institut Pasteur de Montevideo, Montevideo 11400, Uruguay, University of California, San Francisco, San Francisco, CA 94143, USA.
Arlinet
A
Kierbel
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Torsten
T
Wittmann
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Ross J
RJ
Metzger
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Keith E
KE
Mostov
Division of Infectious Disease, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jengel@medicine.ucsf.edu.
Joanne N
JN
Engel
D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D011552:Pseudomonas Infections / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000276:immunology
D002352:Carrier Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D020830:rac1 GTP-Binding Protein; C472451:Pard3 protein, rat; C107953:RAC1 protein, human