ABSTRACT Little is known of how and where bacterial recognition triggers the induction of type I interferon. Whether the type of recognition receptor used in these responses is determined by

the subcellular location of bacteria is not understood. Here we show that phagosomal bacteria such as group B streptococcus, but not cytosolic bacteria, potently induced interferon in

conventional dendritic cells by a mechanism that required Toll-like receptor 7, the adaptor MyD88 and the transcription factor IRF1, all of which localized together with bacterial products

in degradative vacuoles bearing lysosomal markers. Thus, this cell type–specific recognition pathway links lysosomal recognition of bacterial RNA with a robust, host-protective interferon

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(2008). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank T. Taniguchi (University of Tokyo) for permission to use _Irf1__−/−_, _Irf3__−/−_ and _Irf7__−/−_ mice; D.

Golenbock, K. Fitzgerald and E. Lien (University of Massachusetts Medical School) for _Irf1__−/−_, _Irf3__−/−_ and _Irf7__−/−_ mice; T. Leanderson (University of Lund) for _Ifnb__−/−_ mice;

G. Grandi (Novartis Vaccines) and D. Portnoy (University of California) for bacterial strains; and F. Ioppolo (Carl Zeiss) for help with fluorescence microscopy. Supported by the Ministero

dell'Università e della Ricerca of Italy (Project 'Innovative vaccine against group A streptococcus'). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The Elie Metchnikoff

Department, University of Messina, Messina, Italy Giuseppe Mancuso, Maria Gambuzza, Angelina Midiri, Carmelo Biondo, Salvatore Papasergi, Giuseppe Teti & Concetta Beninati * Laboratory

of Host Defense, World Premiere International Immunology Frontier Research Center, Osaka University, Suita, Japan Shizuo Akira Authors * Giuseppe Mancuso View author publications You can

also search for this author inPubMed Google Scholar * Maria Gambuzza View author publications You can also search for this author inPubMed Google Scholar * Angelina Midiri View author

publications You can also search for this author inPubMed Google Scholar * Carmelo Biondo View author publications You can also search for this author inPubMed Google Scholar * Salvatore

Papasergi View author publications You can also search for this author inPubMed Google Scholar * Shizuo Akira View author publications You can also search for this author inPubMed Google

Scholar * Giuseppe Teti View author publications You can also search for this author inPubMed Google Scholar * Concetta Beninati View author publications You can also search for this author

inPubMed Google Scholar CONTRIBUTIONS G.M. and A.M., design and performance of _in vivo_ and _in vitro_ infection experiments; M.G., design and performance of microscopy studies; S.P.,

generation of reagents; S.A., provision of experimental models and discussions; G.M., C.Bi., G.T. and C.Be., data analysis and manuscript preparation. CORRESPONDING AUTHOR Correspondence to

Giuseppe Teti. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–4 and Supplementary Table 1 (PDF 547 kb) SUPPLEMENTARY MOVIE 1 Z-stack of optical sections

obtained by structured illumination microscopy (confront Fig. 7a). GBS-infected cDC, were incubated with anti-TLR7 and anti-MyD88 primary antibodies, and with FITC- and Texas Red-labeled

secondary antibodies, respectively. (MOV 1549 kb) SUPPLEMENTARY MOVIE 2 Z-stack of optical sections obtained by structured illumination microscopy (confront Fig. 7b). GBS-infected cDC, were

incubated with anti-TLR7 and anti-IRF1 primary antibodies, and FITC- and Alexa 594-labeled secondary antibodies, respectively. (MOV 1575 kb) SUPPLEMENTARY MOVIE 3 Z-stack of optical sections

obtained by structured illumination microscopy (confront Fig. 7c). GBS-infected cDC, were incubated with anti-IRF1 and anti-MyD88 primary antibodies and with Alexa 488- and Alexa

594-labeled secondary antibodies, respectively. Arrows indicate colocalization of IRF1 with MyD88 in two DNA-negative areas. (MOV 3094 kb) SUPPLEMENTARY MOVIE 4 Z-stack of optical sections

obtained by structured illumination microscopy (confront supplementary Fig. 3a on line). GBS-infected cDC, were incubated with anti-GBS and anti-IRF1 primary antibodies and with FITC- and

Alexa 594-labeled secondary antibodies, respectively. Images show extensive colocalization of GBS antigen with IRF1 in clusters of coalescing, DNA-negative structures. (MOV 1235 kb) RIGHTS

AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Mancuso, G., Gambuzza, M., Midiri, A. _et al._ Bacterial recognition by TLR7 in the lysosomes of conventional

dendritic cells. _Nat Immunol_ 10, 587–594 (2009). https://doi.org/10.1038/ni.1733 Download citation * Received: 20 February 2009 * Accepted: 07 April 2009 * Published: 10 May 2009 * Issue

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