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Immunity

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https://www.readbyqxmd.com/read/28087240/lactobacillus-deficient-cervicovaginal-bacterial-communities-are-associated-with-increased-hiv-acquisition-in-young-south-african-women
#1
Christina Gosmann, Melis N Anahtar, Scott A Handley, Mara Farcasanu, Galeb Abu-Ali, Brittany A Bowman, Nikita Padavattan, Chandni Desai, Lindsay Droit, Amber Moodley, Mary Dong, Yuezhou Chen, Nasreen Ismail, Thumbi Ndung'u, Musie S Ghebremichael, Duane R Wesemann, Caroline Mitchell, Krista L Dong, Curtis Huttenhower, Bruce D Walker, Herbert W Virgin, Douglas S Kwon
Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4(+) T cells compared to those with Lactobacillus crispatus-dominant communities...
January 9, 2017: Immunity
https://www.readbyqxmd.com/read/28087239/on-going-mechanical-damage-from-mastication-drives-homeostatic-th17-cell-responses-at-the-oral-barrier
#2
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 6, 2017: Immunity
https://www.readbyqxmd.com/read/28087238/lymphocyte-circadian-clocks-control-lymph-node-trafficking-and-adaptive-immune-responses
#3
David Druzd, Olga Matveeva, Louise Ince, Ute Harrison, Wenyan He, Christoph Schmal, Hanspeter Herzel, Anthony H Tsang, Naoto Kawakami, Alexei Leliavski, Olaf Uhl, Ling Yao, Leif Erik Sander, Chien-Sin Chen, Kerstin Kraus, Alba de Juan, Sophia Martina Hergenhan, Marc Ehlers, Berthold Koletzko, Rainer Haas, Werner Solbach, Henrik Oster, Christoph Scheiermann
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes...
January 6, 2017: Immunity
https://www.readbyqxmd.com/read/28065837/vagal-regulation-of-group-3-innate-lymphoid-cells-and-the-immunoresolvent-pctr1-controls-infection-resolution
#4
Jesmond Dalli, Romain A Colas, Hildur Arnardottir, Charles N Serhan
Uncovering mechanisms that control immune responses in the resolution of bacterial infections is critical for the development of new therapeutic strategies that resolve infectious inflammation without unwanted side effects. We found that disruption of the vagal system in mice delayed resolution of Escherichia coli infection. Dissection of the right vagus decreased peritoneal group 3 innate lymphoid cell (ILC3) numbers and altered peritoneal macrophage responses. Vagotomy resulted in an inflammatory peritoneal lipid mediator profile characterized by reduced concentrations of pro-resolving mediators, including the protective immunoresolvent PCTR1, along with elevated inflammation-initiating eicosanoids...
January 4, 2017: Immunity
https://www.readbyqxmd.com/read/27986454/reconstruction-of-lps-transfer-cascade-reveals-structural-determinants-within-lbp-cd14-and-tlr4-md2-for-efficient-lps-recognition-and-transfer
#5
Je-Kyung Ryu, Soo Jin Kim, Sang-Hyun Rah, Ji In Kang, Hi Eun Jung, Dongsun Lee, Heung Kyu Lee, Jie-Oh Lee, Beom Seok Park, Tae-Young Yoon, Ho Min Kim
Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, binds Toll-like receptor 4 (TLR4)-MD2 complex and activates innate immune responses. LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14. To define the sequential molecular interactions underlying this transfer, we reconstituted in vitro the entire LPS transfer process from LPS micelles to TLR4-MD2. Using electron microscopy and single-molecule approaches, we characterized the dynamic intermediate complexes for LPS transfer: LBP-LPS micelles, CD14-LBP-LPS micelle, and CD14-LPS-TLR4-MD2 complex...
December 13, 2016: Immunity
https://www.readbyqxmd.com/read/27986456/isoform-specific-expression-and-feedback-regulation-of-e-protein-tcf4-control-dendritic-cell-lineage-specification
#6
Lucja T Grajkowska, Michele Ceribelli, Colleen M Lau, Margaret E Warren, Ioanna Tiniakou, Sandra Nakandakari Higa, Anna Bunin, Hans Haecker, Leonid A Mirny, Louis M Staudt, Boris Reizis
The cell fate decision between interferon-producing plasmacytoid DC (pDC) and antigen-presenting classical DC (cDC) is controlled by the E protein transcription factor TCF4 (E2-2). We report that TCF4 comprises two transcriptional isoforms, both of which are required for optimal pDC development in vitro. The long Tcf4 isoform is expressed specifically in pDCs, and its deletion in mice impaired pDCs development and led to the expansion of non-canonical CD8(+) cDCs. The expression of Tcf4 commenced in progenitors and was further upregulated in pDCs, correlating with stage-specific activity of multiple enhancer elements...
December 8, 2016: Immunity
https://www.readbyqxmd.com/read/27986455/human-innate-lymphoid-cell-subsets-possess-tissue-type-based-heterogeneity-in-phenotype-and-frequency
#7
Yannick Simoni, Michael Fehlings, Henrik N Kløverpris, Naomi McGovern, Si-Lin Koo, Chiew Yee Loh, Shawn Lim, Ayako Kurioka, Joannah R Fergusson, Choong-Leong Tang, Ming Hian Kam, Koh Dennis, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Chan Weng Hoong, Jerry Kok Yen Chan, Maria Curotto de Lafaille, Sriram Narayanan, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow Toh, Henry Kun Kiaang Tan, Rosslyn Anicete, Eng-Huat Tan, Angela Takano, Paul Klenerman, Alasdair Leslie, Daniel S W Tan, Iain Beehuat Tan, Florent Ginhoux, Evan W Newell
Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues...
December 6, 2016: Immunity
https://www.readbyqxmd.com/read/28002731/cholesterol-accumulation-in-cd11c-immune-cells-is-a-causal-and-targetable-factor-in-autoimmune-disease
#8
Ayaka Ito, Cynthia Hong, Kazuhiro Oka, Jon V Salazar, Cody Diehl, Joseph L Witztum, Mercedes Diaz, Antonio Castrillo, Steven J Bensinger, Lawrence Chan, Peter Tontonoz
Liver X receptors (LXRs) are regulators of cholesterol metabolism that also modulate immune responses. Inactivation of LXR α and β in mice leads to autoimmunity; however, how the regulation of cholesterol metabolism contributes to autoimmunity is unclear. Here we found that cholesterol loading of CD11c(+) cells triggered the development of autoimmunity, whereas preventing excess lipid accumulation by promoting cholesterol efflux was therapeutic. LXRβ-deficient mice crossed to the hyperlipidemic ApoE-deficient background or challenged with a high-cholesterol diet developed autoantibodies...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002730/inhaled-fine-particles-induce-alveolar-macrophage-death-and-interleukin-1%C3%AE-release-to-promote-inducible-bronchus-associated-lymphoid-tissue-formation
#9
Etsushi Kuroda, Koji Ozasa, Burcu Temizoz, Keiichi Ohata, Christine X Koo, Tomohiro Kanuma, Takato Kusakabe, Shingo Kobari, Masanori Horie, Yasuo Morimoto, Saeko Nakajima, Kenji Kabashima, Steven F Ziegler, Yoichiro Iwakura, Wataru Ise, Tomohiro Kurosaki, Takahiro Nagatake, Jun Kunisawa, Naoki Takemura, Satoshi Uematsu, Masayuki Hayashi, Taiki Aoshi, Kouji Kobiyama, Cevayir Coban, Ken J Ishii
Particulate pollution is thought to function as an adjuvant that can induce allergic responses. However, the exact cell types and immunological factors that initiate the lung-specific immune responses are unclear. We found that upon intratracheal instillation, particulates such as aluminum salts and silica killed alveolar macrophages (AMs), which then released interleukin-1α (IL-1α) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1α release continued for up to 2 weeks after particulate exposure, and type-2 allergic immune responses were induced by the inhalation of antigen during IL-1α release and iBALT formation, even long after particulate instillation...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002729/the-heterogeneity-of-ly6c-hi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells
#10
Shinelle Menezes, Daisy Melandri, Giorgio Anselmi, Thibaut Perchet, Jakob Loschko, Juan Dubrot, Rajen Patel, Emmanuel L Gautier, Stéphanie Hugues, M Paula Longhi, Jake Y Henry, Sergio A Quezada, Grégoire Lauvau, Ana-Maria Lennon-Duménil, Enrique Gutiérrez-Martínez, Alain Bessis, Elisa Gomez-Perdiguero, Christian E Jacome-Galarza, Hannah Garner, Frederic Geissmann, Rachel Golub, Michel C Nussenzweig, Pierre Guermonprez
Inflammation triggers the differentiation of Ly6C(hi) monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3(+)CD11c(-)MHCII(+)PU.1(hi) subset...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002728/expanding-the-immunology-toolbox-embracing-public-data-reuse-and-crowdsourcing
#11
REVIEW
Rachel Sparks, William W Lau, John S Tsang
New technologies have been propelling dramatic increases in the volume and diversity of large-scale public data, which can potentially be reused to answer questions beyond those originally envisioned. However, this often requires computational and statistical skills beyond the reach of most bench scientists. The development of educational and accessible computational tools is thus critical, as are crowdsourcing efforts that utilize the community's expertise to curate public data for hypothesis generation and testing...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002727/allergen-exposure-when-timing-is-everything
#12
Tanel Mahlakõiv, David Artis
It is known that young children exposed to allergens are prone to develop asthma later in life. In this issue of Immunity, de Kleer et al. (2016) identify IL-33 as a key player in the developing lung for sensitization to environmental allergens and airway hyperreactivity.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002726/immune-cell-intolerance-for-excess-cholesterol
#13
Scott B Widenmaier, Gökhan S Hotamışlıgil
Chronic metabolic challenges have severe consequences on physiological systems. In this issue of Immunity, Ito et al. (2016) show that defects in cholesterol metabolism in CD11c(+) immune cells result in impaired antigen presentation and ultimately in autoimmune disease.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002725/sifting-through-cd8-t-cell-memory
#14
Matthew D Martin, Vladimir P Badovinac
In this issue of Immunity, Gerlach et al. (2016) describe three distinct memory CD8(+) T cell subsets based upon expression of the fractalkine receptor CX3CR1. Their findings revise the paradigm of effector and central memory T cells by revealing a subset of CD8(+) memory T cells defined by intermediate levels of expression of CX3CR1 that conducts tissue surveillance.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002724/too-much-of-a-good-thing-chronic-ifn-fuels-resistance-to-cancer-immunotherapy
#15
James L Reading, Sergio A Quezada
Immune checkpoint blockade (ICB) is revolutionizing cancer medicine, yet the molecular basis of resistance remains unclear. In a recent issue of Cell, Benci et al. (2016) demonstrate that sustained interferon signaling is central to the development of PD-L1-dependent and -independent resistance to ICB.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002723/precision-targeting-mast-cells-wipe-out-infected-bladder-epithelia
#16
Hongnga T Le, Booki Min
Exfoliating infected bladder epithelium is a powerful host defense mechanism that reduces bacterial burden. In this issue of Immunity, Choi et al. (2016) present a function of mast cells that orchestrates the infected epithelial cell exfoliation via cytolytic granules.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/28002722/one-niche-to-rule-both-maintenance-and-loss-of-stemness-in-hscs
#17
Motonari Kondo
Hemato-lymphopoiesis initiated by hematopoietic stem cells (HSCs) is tightly regulated by factors present in the bone marrow (BM) niche. Using genetically modified mice, Gomes et al. (2016) show that IL-7 is produced by HSC niche-forming cells and find that the same niche that controls HSC self-renewal can also support differentiation.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27986453/cd8-t-cells-utilize-highly-dynamic-enhancer-repertoires-and-regulatory-circuitry-in-response-to-infections
#18
Bing He, Shaojun Xing, Changya Chen, Peng Gao, Li Teng, Qiang Shan, Jodi A Gullicksrud, Matthew D Martin, Shuyang Yu, John T Harty, Vladimir P Badovinac, Kai Tan, Hai-Hui Xue
Differentiation of effector and memory CD8(+) T cells is accompanied by extensive changes in the transcriptome and histone modifications at gene promoters; however, the enhancer repertoire and associated gene regulatory networks are poorly defined. Using histone mark chromatin immunoprecipitation coupled with deep sequencing, we mapped the enhancer and super-enhancer landscapes in antigen-specific naive, differentiated effector, and central memory CD8(+) T cells during LCMV infection. Epigenomics-based annotation revealed a highly dynamic repertoire of enhancers, which were inherited, de novo activated, decommissioned and re-activated during CD8(+) T cell responses...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27939674/loss-of-bladder-epithelium-induced-by-cytolytic-mast-cell-granules
#19
Hae Woong Choi, Samantha E Bowen, Yuxuan Miao, Cheryl Y Chan, Edward A Miao, Magnus Abrink, Adam J Moeser, Soman N Abraham
Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cystitis, shedding of infected bladder epithelial cells (BECs) was preceded by the recruitment of mast cells (MCs) directly underneath the superficial epithelium where they docked and extruded their granules. MCs were responding to interleukin-1β (IL-1β) secreted by BECs after inflammasome and caspase-1 signaling...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27939673/perinatal-activation-of-the-interleukin-33-pathway-promotes-type-2-immunity-in-the-developing-lung
#20
Ismé M de Kleer, Mirjam Kool, Marjolein J W de Bruijn, Monique Willart, Justine van Moorleghem, Martijn J Schuijs, Maud Plantinga, Rudi Beyaert, Emily Hams, Padraic G Fallon, Hamida Hammad, Rudi W Hendriks, Bart N Lambrecht
Allergic disease originates in early life and polymorphisms in interleukin-33 gene (IL33) and IL1RL1, coding for IL-33R and decoy receptor sST2, confer allergy risk. Early life T helper 2 (Th2) cell skewing and allergy susceptibility are often seen as remnants of feto-maternal symbiosis. Here we report that shortly after birth, innate lymphoid type 2 cells (ILC2s), eosinophils, basophils, and mast cells spontaneously accumulated in developing lungs in an IL-33-dependent manner. During the phase of postnatal lung alveolarization, house dust mite exposure further increased IL-33, which boosted cytokine production in ILC2s and activated CD11b(+) dendritic cells (DCs)...
December 20, 2016: Immunity
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