Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection

Cindy S. Tran; Yoni Eran; Travis R. Ruch; David M. Bryant; Anirban Datta; Paul Brakeman; Arlinet Kierbel; Torsten Wittmann; Ross J. Metzger; Keith E. Mostov; Joanne N. Engel

doi:10.1016/j.chom.2014.04.007

Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection

Cindy S. Tran, Yoni Eran, Travis R. Ruch, David M. Bryant, Anirban Datta, Paul Brakeman, Arlinet Kierbel, Torsten Wittmann, Ross J. Metzger, Keith E. Mostov, Joanne N. Engel

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37 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	636-643
Number of pages	8
Journal	Cell Host and Microbe
Volume	15
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2014.04.007
State	Published - 14 May 2014
Externally published	Yes

Bibliographical note

Funding Information:
We thank Kurt Thorn and the UCSF Nikon Imaging Center for assistance with microscopy. Financial support was provided by EMBO (Y.E.), NIH RO1 AI065902 (J.N.E.), PO1 AI53194 (J.N.E. and K.E.M.), K99CA163535 (D.M.B), K12 HD072222 (C.S.T.), K12 HD000850 (C.S.T.), and K08 DK068358 (P.B.).

Funding

We thank Kurt Thorn and the UCSF Nikon Imaging Center for assistance with microscopy. Financial support was provided by EMBO (Y.E.), NIH RO1 AI065902 (J.N.E.), PO1 AI53194 (J.N.E. and K.E.M.), K99CA163535 (D.M.B), K12 HD072222 (C.S.T.), K12 HD000850 (C.S.T.), and K08 DK068358 (P.B.).

Funders	Funder number
National Institutes of Health	K08 DK068358, PO1 AI53194, K12 HD000850, RO1 AI065902, K99CA163535, K12 HD072222
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK074398
European Molecular Biology Organization

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title = "Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection",

abstract = "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.",

author = "Tran, {Cindy S.} and Yoni Eran and Ruch, {Travis R.} and Bryant, {David M.} and Anirban Datta and Paul Brakeman and Arlinet Kierbel and Torsten Wittmann and Metzger, {Ross J.} and Mostov, {Keith E.} and Engel, {Joanne N.}",

note = "Funding Information: We thank Kurt Thorn and the UCSF Nikon Imaging Center for assistance with microscopy. Financial support was provided by EMBO (Y.E.), NIH RO1 AI065902 (J.N.E.), PO1 AI53194 (J.N.E. and K.E.M.), K99CA163535 (D.M.B), K12 HD072222 (C.S.T.), K12 HD000850 (C.S.T.), and K08 DK068358 (P.B.). ",

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AU - Tran, Cindy S.

AU - Eran, Yoni

AU - Ruch, Travis R.

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AU - Datta, Anirban

AU - Brakeman, Paul

AU - Kierbel, Arlinet

AU - Wittmann, Torsten

AU - Metzger, Ross J.

AU - Mostov, Keith E.

AU - Engel, Joanne N.

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PY - 2014/5/14

Y1 - 2014/5/14

N2 - 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.

AB - 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.

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Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection

Abstract

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