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

Research output: Contribution to journalArticlepeer-review

36 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 languageEnglish
Pages (from-to)636-643
Number of pages8
JournalCell Host and Microbe
Volume15
Issue number5
DOIs
StatePublished - 14 May 2014
Externally publishedYes

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.).

FundersFunder number
National Institutes of HealthK08 DK068358, PO1 AI53194, K12 HD000850, RO1 AI065902, K99CA163535, K12 HD072222
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK074398
European Molecular Biology Organization

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