Bacterial recognition by TLR7 in the lysosomes   of conventional dendritic cells.
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 response.
Mancuso
Giuseppe
G
The Elie Metchnikoff Department, University of Messina, Messina, Italy.
Gambuzza
Maria
M
Midiri
Angelina
A
Biondo
Carmelo
C
Papasergi
Salvatore
S
Akira
Shizuo
S
Teti
Giuseppe
G
Beninati
Concetta
C
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D050856:Interferon Regulatory Factor-1 / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism; D012329:RNA, Bacterial / Q000378:metabolism; D015398:Signal Transduction; D013290:Streptococcal Infections / Q000276:immunology; D013292:Streptococcus agalactiae / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology / Q000378:metabolism*
D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012329:RNA, Bacterial; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D016899:Interferon-beta