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Nicholas Collins, Yasmine Belkaid
The reliance of the immune system on constitutive microbial stimulation support the idea that both responsiveness to vaccines and vaccine design need to be considered in the context of host-microbiota interactions. Manipulation of microbe function or composition via diet alteration or microbiota engraftment may soon become a viable approach to control immunity and, as such, vaccine responses. Learning from our endogenous original adjuvants could be critical in overcoming the enormous hurdle of vaccine design against the numerous pathogens that cause chronic infection...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
Yasmine Belkaid, Oliver J Harrison
The microbiota plays a fundamental role in the induction, education, and function of the host immune system. In return, the host immune system has evolved multiple means by which to maintain its symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and the utilization of regulatory pathways involved in the sustained tolerance to innocuous antigens. The ability of microbes to set the immunological tone of tissues, both locally and systemically, requires tonic sensing of microbes and complex feedback loops between innate and adaptive components of the immune system...
April 18, 2017: Immunity
Ha-Na Lee, Linjie Tian, Nicolas Bouladoux, Jacquice Davis, Mariam Quinones, Yasmine Belkaid, John E Coligan, Konrad Krzewski
Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut...
April 17, 2017: Journal of Clinical Investigation
Anissa Belkaid, Rodney J Ouellette, Marc E Surette
Long chain acyl-CoA synthase-4 (ACSL4) expression has been associated with an aggressive phenotype in breast carcinoma cells, whereas its role in ERα-positive breast cancer has not been studied. ACSL4 prefers 20-carbon polyunsaturated fatty acid (PUFA) substrates, and along with other ACSLs has been associated with cellular uptake of exogenous fatty acids. 17β-estradiol induces proliferation and invasive capacities in ERα+ve breast carcinoma that is associated with modifications of cellular lipid metabolism...
April 1, 2017: Carcinogenesis
Nicolas Dutzan, Loreto Abusleme, Hayley Bridgeman, Teresa Greenwell-Wild, Tamsin Zangerle-Murray, Mark E Fife, Nicolas Bouladoux, Holly Linley, Laurie Brenchley, Kelly Wemyss, Gloria Calderon, Bo-Young Hong, Timothy J Break, Dawn M E Bowdish, Michail S Lionakis, Simon A Jones, Giorgio Trinchieri, Patricia I Diaz, Yasmine Belkaid, Joanne E Konkel, Niki M Moutsopoulos
Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism...
January 17, 2017: Immunity
Nicolas Bouladoux, Clotilde Hennequin, Camille Malosse, Bernard Malissen, Yasmine Belkaid, Sandrine Henri
Hapten-specific T cell-mediated skin inflammation also known as contact hypersensitivity (CHS) is characterized by a strong influx of CD8(+) cytotoxic T cells within the skin upon reexposure of sensitized individuals to the same hapten. As many other leukocytes are also recruited during this elicitation phase, we attempted to revisit the skin infiltrate and characterize the inflammatory pattern. Recent improvement in the isolation in conventional as well as inflammatory dendritic cell and macrophage subsets from tissues and in the use of appropriate surface markers unraveling their heterogeneity should allow to determinate their specific functions in the CHS model...
2017: Methods in Molecular Biology
Chiaki Iwamura, Nicolas Bouladoux, Yasmine Belkaid, Alan Sher, Dragana Jankovic
The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characterized. We observed that stimulation with NOD1 or NOD2 ligand had no effect on the survival/proliferation of hematopoietic precursors. Nonetheless, NOD1, but not NOD2, ligand induced expression of multiple hematopoietic cytokines (interleukin-7 [IL-7], Flt3L, stem cell factor [SCF], ThPO, and IL-6) from bone marrow mesenchymal stromal cells (MSCs) in vitro...
January 12, 2017: Blood
Aleksey Chudnovskiy, Arthur Mortha, Veronika Kana, Andrea Kennard, Juan David Ramirez, Adeeb Rahman, Romain Remark, Ilaria Mogno, Ruby Ng, Sasha Gnjatic, El-Ad David Amir, Alexander Solovyov, Benjamin Greenbaum, Jose Clemente, Jeremiah Faith, Yasmine Belkaid, Michael E Grigg, Miriam Merad
While conventional pathogenic protists have been extensively studied, there is an underappreciated constitutive protist microbiota that is an integral part of the vertebrate microbiome. The impact of these species on the host and their potential contributions to mucosal immune homeostasis remain poorly studied. Here, we show that the protozoan Tritrichomonas musculis activates the host epithelial inflammasome to induce IL-18 release. Epithelial-derived IL-18 promotes dendritic cell-driven Th1 and Th17 immunity and confers dramatic protection from mucosal bacterial infections...
October 6, 2016: Cell
Timothy W Hand, Ivan Vujkovic-Cvijin, Vanessa K Ridaura, Yasmine Belkaid
Chronic inflammatory diseases (CIDs) are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many CIDs are associated with significant shifts in the microbiota toward inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites...
December 2016: Trends in Endocrinology and Metabolism: TEM
David Clever, Rahul Roychoudhuri, Michael G Constantinides, Michael H Askenase, Madhusudhanan Sukumar, Christopher A Klebanoff, Robert L Eil, Heather D Hickman, Zhiya Yu, Jenny H Pan, Douglas C Palmer, Anthony T Phan, John Goulding, Luca Gattinoni, Ananda W Goldrath, Yasmine Belkaid, Nicholas P Restifo
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function...
August 25, 2016: Cell
Christoph Wilhelm, Oliver J Harrison, Vanessa Schmitt, Martin Pelletier, Sean P Spencer, Joseph F Urban, Michelle Ploch, Thirumalai R Ramalingam, Richard M Siegel, Yasmine Belkaid
Innate lymphoid cells (ILC) play an important role in many immune processes, including control of infections, inflammation, and tissue repair. To date, little is known about the metabolism of ILC and whether these cells can metabolically adapt in response to environmental signals. Here we show that type 2 innate lymphoid cells (ILC2), important mediators of barrier immunity, predominantly depend on fatty acid (FA) metabolism during helminth infection. Further, in situations where an essential nutrient, such as vitamin A, is limited, ILC2 sustain their function and selectively maintain interleukin 13 (IL-13) production via increased acquisition and utilization of FA...
July 25, 2016: Journal of Experimental Medicine
Anissa Belkaid, Miroslava Čuperlović-Culf, Mohamed Touaibia, Rodney J Ouellette, Marc E Surette
Metabolic shift is one of the major hallmarks of cancer development. Estrogen receptor (ER) activity has a profound effect on breast cancer cell growth through a number of metabolic changes driven by its effect on transcription of several enzymes, including carbonic anhydrases, Stearoyl-CoA desaturase-1, and oncogenes including HER2. Thus, estrogen receptor activators can be expected to lead to the modulation of cell metabolism in estrogen receptor positive cells. In this work we have investigated the effect of 17β-estradiol, an ER activator, and ferulic acid, a carbonic anhydrase inhibitor, as well as ER activator, in the absence and in the presence of the carbonic anhydrase inhibitor acetazolamide on the metabolism of MCF7 cells and MCF7 cells, stably transfected to express HER2 (MCF7HER2)...
2016: Metabolites
Yasmine Belkaid, Samira Tamoutounour
The skin is a complex and dynamic ecosystem that is inhabited by many microorganisms. Recent evidence highlights the profound reliance of the skin immune system on its resident microbiota for both host defence and tissue repair. This tissue is also a primary target for infections, which are in some cases caused by normal constituents of the microbiota. In the context of infections and genetic predispositions that are associated with barrier or regulatory network defects, microorganism-induced inflammatory cycles can contribute to the initiation and/or amplification of skin disorders...
May 27, 2016: Nature Reviews. Immunology
Justin P Edwards, Timothy W Hand, Denise Morais da Fonseca, Deborah D Glass, Yasmine Belkaid, Ethan M Shevach
Treg cells can secrete latent TGF-β1 (LTGF-β1), but can also utilize an alternative pathway for transport and expression of LTGF-β1 on the cell surface in which LTGF-β1 is coupled to a distinct LTGF-β binding protein termed glycoprotein A repetitions predominant (GARP)/LRRC32. The function of the GARP/LTGF-β1 complex has remained elusive. Here, we examine in vivo the roles of GARP and TGF-β1 in the induction of oral tolerance. When Foxp3(-) OT-II T cells were transferred to wild-type recipient mice followed by OVA feeding, the conversion of Foxp3(-) to Foxp3(+) OT-II cells was dependent on recipient Treg cells...
June 2016: European Journal of Immunology
Chao Zhong, Kairong Cui, Christoph Wilhelm, Gangqing Hu, Kairui Mao, Yasmine Belkaid, Keji Zhao, Jinfang Zhu
No abstract text is available yet for this article.
April 2016: Nature Immunology
Chao Zhong, Kairong Cui, Christoph Wilhelm, Gangqing Hu, Kairui Mao, Yasmine Belkaid, Keji Zhao, Jinfang Zhu
No abstract text is available yet for this article.
February 2016: Nature Immunology
Chao Zhong, Kairong Cui, Christoph Wilhelm, Gangqing Hu, Kairui Mao, Yasmine Belkaid, Keji Zhao, Jinfang Zhu
The transcription factor GATA-3 is indispensable for the development of all innate lymphoid cells (ILCs) that express the interleukin 7 receptor α-chain (IL-7Rα). However, the function of low GATA-3 expression in committed group 3 ILCs (ILC3 cells) has not been identified. We found that GATA-3 regulated the homeostasis of ILC3 cells by controlling IL-7Rα expression. In addition, GATA-3 served a critical function in the development of the NKp46(+) ILC3 subset by regulating the balance between the transcription factors T-bet and RORγt...
February 2016: Nature Immunology
Abdelhakim Belkaid, Abdelhalim Kessal, Jean-Paul Gaubert, Ahmed Gherbi
No abstract text is available yet for this article.
January 2016: ISA Transactions
Denise Morais da Fonseca, Timothy W Hand, Seong-Ji Han, Michael Y Gerner, Arielle Glatman Zaretsky, Allyson L Byrd, Oliver J Harrison, Alexandra M Ortiz, Mariam Quinones, Giorgio Trinchieri, Jason M Brenchley, Igor E Brodsky, Ronald N Germain, Gwendalyn J Randolph, Yasmine Belkaid
Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node...
October 8, 2015: Cell
Elizabeth A Wohlfert, Andrea C Carpenter, Yasmine Belkaid, Rémy Bosselut
In vitro culture is an important complement, or substitute, to in vivo approaches in order to study T cell effector differentiation. Here, we describe culture conditions that generate specific effector cell types by exposing naïve T cells to appropriate cytokine signals.
2016: Methods in Molecular Biology
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