Conventional Dendritic Cells Mount a Type I IFN Response against Candida spp. Requiring Novel Phagosomal TLR7-Mediated IFN-β Signaling
Christelle Bourgeois,Olivia Majer,Ingrid E. Frohner,Iwona Lesiak-Markowicz,Kwang-Soo Hildering,Walter Glaser,Silvia Stockinger,Thomas Decker,Shizuo Akira,Mathias Müller,Karl Kuchler +10 more
TLDR
In this article, the authors demonstrate a mechanism mediating a strong IFN-β response in mouse conventional dendritic cells challenged by Candida spp., subsequently orchestrating IFNα/β receptor 1-dependent intracellular STAT1 activation and IFN regulatory factor (IRF) 7 expression.Abstract:
Human fungal pathogens such as the dimorphic Candida albicans or the yeast-like Candida glabrata can cause systemic candidiasis of high mortality in immunocompromised individuals. Innate immune cells such as dendritic cells and macrophages establish the first line of defense against microbial pathogens and largely determine the outcome of infections. Among other cytokines, they produce type I IFNs (IFNs-I), which are important modulators of the host immune response. Whereas an IFN-I response is a hallmark immune response to bacteria and viruses, a function in fungal pathogenesis has remained unknown. In this study, we demonstrate a novel mechanism mediating a strong IFN-β response in mouse conventional dendritic cells challenged by Candida spp., subsequently orchestrating IFN-α/β receptor 1-dependent intracellular STAT1 activation and IFN regulatory factor (IRF) 7 expression. Interestingly, the initial IFN-β release bypasses the TLR 4 and TLR2, the TLR adaptor Toll/IL-1R domain-containing adapter-inducing IFN-β and the β-glucan/phagocytic receptors dectin-1 and CD11b. Notably, Candida-induced IFN-β release is strongly impaired by Src and Syk family kinase inhibitors and strictly requires completion of phagocytosis as well as phagosomal maturation. Strikingly, TLR7, MyD88, and IRF1 are essential for IFN-β signaling. Furthermore, in a mouse model of disseminated candidiasis we show that IFN-I signaling promotes persistence of C. glabrata in the host. Our data uncover for the first time a pivotal role for endosomal TLR7 signaling in fungal pathogen recognition and highlight the importance of IFNs-I in modulating the host immune response to C. glabrata.read more
Citations
More filters
Journal ArticleDOI
Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity
Taro Kawai,Shizuo Akira +1 more
TL;DR: The role played by TLRs in mounting protective immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition is focused on.
Journal ArticleDOI
Type I interferons in infectious disease.
TL;DR: Experimental models of tuberculosis have demonstrated that prostaglandin E2 and interleukin-1 inhibit type I IFN expression and its downstream effects, demonstrating that a cross-regulatory network of cytokines operates during infectious diseases to provide protection with minimum damage to the host.
Journal ArticleDOI
C-type lectins in immunity: recent developments.
Ivy M. Dambuza,Gordon D. Brown +1 more
TL;DR: CLRs play an essential role in immunity to fungi and mycobacteria and are involved in the regulation of homeostasis, autoimmunity and allergy.
Journal ArticleDOI
C-type lectin receptors orchestrate antifungal immunity
TL;DR: Recent advances in the understanding of the roles and mechanisms of these multifunctional receptors are highlighted, how these PRRs orchestrate antifungal immunity is explored and progress in the use of these receptors as targets for antifundal and other vaccines is discussed.
Journal ArticleDOI
Immune defence against Candida fungal infections
Mihai G. Netea,Leo A. B. Joosten,Jos W. M. van der Meer,Bart Jan Kullberg,Frank L. van de Veerdonk +4 more
TL;DR: How innate sensing of fungi by pattern recognition receptors and the interplay of immune cells (both myeloid and lymphoid) with non-immune cells, including platelets and epithelial cells, shapes host immunity to Candida species is described.
References
More filters
Journal ArticleDOI
A Toll-like receptor recognizes bacterial DNA.
Hiroaki Hemmi,Osamu Takeuchi,Taro Kawai,Tsuneyasu Kaisho,Shintaro Sato,Hideki Sanjo,Makoto Matsumoto,Katsuaki Hoshino,Hermann Wagner,Kiyoshi Takeda,Shizuo Akira +10 more
TL;DR: It is shown that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9, and vertebrate immune systems appear to have evolved a specific Toll- like receptor that distinguishes bacterial DNA from self-DNA.
Journal ArticleDOI
Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data.
TL;DR: It is shown that the first approach can lead to PCR efficiencies that vary over a 0.2 range, whereas the second approach may be off by 0.26, and proposed linear regression on the Log(fluorescence) per cycle number data as an assumption-free method to calculate starting concentrations of mRNAs and PCRefficiencies for each sample.
Journal Article
Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
Katsuaki Hoshino,Osamu Takeuchi,Taro Kawai,Hideki Sanjo,Tomohiko Ogawa,Yoshifumi Takeda,Kiyoshi Takeda,Shizuo Akira +7 more
TL;DR: It is demonstrated that TLR4 is the gene product that regulates LPS response, and a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family is found.
Journal ArticleDOI
Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.
Osamu Takeuchi,Katsuaki Hoshino,Taro Kawai,Hideki Sanjo,Haruhiko Takada,Tomohiko Ogawa,Kiyoshi Takeda,Shizuo Akira +7 more
TL;DR: It is demonstrated that TLR2 and TLR4 recognize different bacterial cell wall components in vivo andTLR2 plays a major role in Gram-positive bacterial recognition.
Journal ArticleDOI
Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway.
Hiroaki Hemmi,Tsuneyasu Kaisho,Osamu Takeuchi,Shintaro Sato,Hideki Sanjo,Katsuaki Hoshino,Takao Horiuchi,Hideyuki Tomizawa,Kiyoshi Takeda,Shizuo Akira +9 more
TL;DR: It is shown that the imidazoquinolines activate immune cells via the Toll-like receptor 7 (TLR7)-MyD88–dependent signaling pathway, and that neither MyD88- nor TLR7-deficient mice showed any inflammatory cytokine production by macrophages, proliferation of splenocytes or maturation of dendritic cells.
Related Papers (5)
Dectin-2 Recognition of α-Mannans and Induction of Th17 Cell Differentiation Is Essential for Host Defense against Candida albicans
Shinobu Saijo,Satoshi Ikeda,Keiko Yamabe,Shigeru Kakuta,Harumichi Ishigame,Aoi Akitsu,Noriyuki Fujikado,Toshimasa Kusaka,Sachiko Kubo,Soo Hyun Chung,Ryohei Komatsu,Noriko Miura,Yoshiyuki Adachi,Naohito Ohno,Kazutoshi Shibuya,Natsuo Yamamoto,Kazuyoshi Kawakami,Sho Yamasaki,Takashi Saito,Shizuo Akira,Yoichiro Iwakura +20 more
Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections
Bart Ferwerda,Gerben Ferwerda,Theo S. Plantinga,Janet A. Willment,Annemiek B. van Spriel,Hanka Venselaar,Clara C. Elbers,Melissa D. Johnson,Alessandra Cambi,Cristal Huysamen,Liesbeth Jacobs,Trees Jansen,Karlijn Verheijen,Laury J.N. Masthoff,Servaas A. Morré,Gert Vriend,David L. Williams,John R. Perfect,Leo A. B. Joosten,Cisca Wijmenga,Jos W. M. van der Meer,Gosse J. Adema,Bart Jan Kullberg,Gordon D. Brown,Mihai G. Netea +24 more