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Immunity
This journal offers authors two options (open access or subscription) to publish research

Jun 21, 2016

Volume 44Issue 6p1241-1470
Open Archive
On the cover: Aedes aegypti mosquitoes transmit many viruses that affect human health, including those that cause Zika virus disease and dengue fever. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. In this issue of Immunity, Pingen et al. show that the mosquito bite causes the mammalian host to mount an inflammatory response that aids viral replication and dissemination, resulting in a more severe infection than that which occurs when the virus is inoculated into unbitten skin. The cover depicts this initiating event of abovirus transmission, when a mosquito bites mammalian skin, injects virus, and causes an inflammatory response that is ultimately detrimental to the host. Image by Steven Bryden....
On the cover: Aedes aegypti mosquitoes transmit many viruses that affect human health, including those that cause Zika virus disease and dengue fever. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. In this issue of Immunity, Pingen et al. show that the mosquito bite causes the mammalian host to mount an inflammatory response that aids viral replication and dissemination, resulting in a more severe infection than that which occurs when the virus is inoculated into unbitten skin. The cover depicts this initiating event of abovirus transmission, when a mosquito bites mammalian skin, injects virus, and causes an inflammatory response that is ultimately detrimental to the host. Image by Steven Bryden.

Previews

  • Fine-Tuning Th17 Cells: To Be or Not To Be Pathogenic?

    • Chrysi Kanellopoulou,
    • Stefan A. Muljo
    Like the story of Jekyll and Hyde, Th17 cells have two guises. One helps with host immunity, but the other can cause immunopathology. In this issue of Immunity, Dong and colleagues report that three microRNAs, miR-183, miR-96, and miR-182, can switch on the pathogenicity of Th17 cells (Ichiyama et al., 2016).
  • InterFeriNg with Acetγlation: Stress-Levels of Acetate Improve Memory T Cell Function

    • Caroline A. Lewis,
    • Matthew G. Vander Heiden
    Catabolic stress can lead to changes in circulating acetate levels. Hess and colleagues (2016) report that serum acetate increases in response to acute infection and describe a mechanism by which this results in acetylation of the glycolytic enzyme GAPDH and improves the recall function of memory CD8+ T cells.
  • pDCs Take a Deep Breath to Fight Viruses

    • Luciana Berod,
    • Tim Sparwasser
    Conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) serve non-overlapping functions in immune responses. Pearce and colleagues (2016) report that pDCs use different metabolic pathways from cDCs to support their specialized function.
  • Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer

    • Ada G. Blidner,
    • Karina V. Mariño,
    • Gabriel A. Rabinovich
    Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1.
  • Battling the Bite: Tradeoffs in Immunity to Insect-Borne Pathogens

    • David Samuel Schneider
    Effective pathogens are successful, by definition, because they can defeat our immune response. Pingen et al. (2016) in this issue of Immunity demonstrate that some mosquito-transmitted viruses depend upon a strong host immune response triggered by the innate immune response to the bite to promote dissemination through the body.
  • Broadly Neutralizing Antibodies: Magic Bullets against HIV?

    • Boris Julg,
    • Galit Alter
    Broadly neutralizing antibodies (bNAbs) offer new avenues for HIV prevention and cure strategies. Three recent papers, published in Science and Nature, highlight the broad applicability of bNAbs in HIV cure and prevention and in boosting immunity against HIV.

Review

Articles

  • The Costimulatory Receptor OX40 Inhibits Interleukin-17 Expression through Activation of Repressive Chromatin Remodeling Pathways

    • Xiang Xiao,
    • Xiaomin Shi,
    • Yihui Fan,
    • Chenglin Wu,
    • Xiaolong Zhang,
    • Laurie Minze,
    • Wentao Liu,
    • Rafik M. Ghobrial,
    • Peixiang Lan,
    • Xian Chang Li
    IL-17-producing Th17 cells are involved in multiple autoimmune diseases. Li and colleagues find that the costimulatory receptor OX40 inhibits IL-17 expression and Th17 cell-mediated autoimmunity by inducing repressive chromatin modifications at Il17 locus by activation of histone methyltransferases G9a and SETDB1.
  • The MicroRNA-183-96-182 Cluster Promotes T Helper 17 Cell Pathogenicity by Negatively Regulating Transcription Factor Foxo1 Expression

    • Kenji Ichiyama,
    • Alicia Gonzalez-Martin,
    • Byung-Seok Kim,
    • Hyun Yong Jin,
    • Wei Jin,
    • Wei Xu,
    • Mohsen Sabouri-Ghomi,
    • Shunbin Xu,
    • Pan Zheng,
    • Changchun Xiao,
    • Chen Dong
    Epigenetic regulation is important for T cell differentiation. However, the roles of miRNAs in Th17 cell development and function are unclear. Dong and colleagues identify miR-183C as a pathogenic Th17-cell-specific miRNA and demonstrate that miR-183C promotes Th17 cell pathogenicity via suppression of Foxo1 expression.
  • Fine-Tuning of CD8+ T Cell Mitochondrial Metabolism by the Respiratory Chain Repressor MCJ Dictates Protection to Influenza Virus

    • Devin P. Champagne,
    • Ketki M. Hatle,
    • Karen A. Fortner,
    • Angelo D’Alessandro,
    • Tina M. Thornton,
    • Rui Yang,
    • Daniel Torralba,
    • Julen Tomás-Cortázar,
    • Yong Woong Jun,
    • Kyo Han Ahn,
    • Kirk C. Hansen,
    • Laura Haynes,
    • Juan Anguita,
    • Mercedes Rincon
    The endogenous molecular mechanisms controlling mitochondrial respiration in CD8+ T cells are not fully understood. In this issue of Immunity, Rincon and colleagues reveal that MCJ is a negative regulator of mitochondrial respiration in CD8+ T cells. Loss of MCJ enhances protective activity of memory CD8+ T cells against influenza virus.
  • Memory CD8+ T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function

    • Maria L. Balmer,
    • Eric H. Ma,
    • Glenn R. Bantug,
    • Jasmin Grählert,
    • Simona Pfister,
    • Timo Glatter,
    • Annaïse Jauch,
    • Sarah Dimeloe,
    • Emma Slack,
    • Philippe Dehio,
    • Magdalena A. Krzyzaniak,
    • Carolyn G. King,
    • Anne-Valérie Burgener,
    • Marco Fischer,
    • Leyla Develioglu,
    • Réka Belle,
    • Mike Recher,
    • Weldy V. Bonilla,
    • Andrew J. Macpherson,
    • Siegfried Hapfelmeier,
    • Russell G. Jones,
    • Christoph Hess
    How systemic metabolic alterations during acute infections impact immune-cell function remains poorly understood. Hess and colleagues demonstrate that acetate rapidly increases during infections, which drives acetylation of GAPDH in memory CD8+ T cells and thereby catalyzes the rapid recall response.
  • Type 1 Interferons Induce Changes in Core Metabolism that Are Critical for Immune Function

    • Duojiao Wu,
    • David E. Sanin,
    • Bart Everts,
    • Qiongyu Chen,
    • Jing Qiu,
    • Michael D. Buck,
    • Annette Patterson,
    • Amber M. Smith,
    • Chih-Hao Chang,
    • Zhiping Liu,
    • Maxim N. Artyomov,
    • Erika L. Pearce,
    • Marina Cella,
    • Edward J. Pearce
    Type 1 IFN cytokines play complex and incompletely understood roles in immunity. Pearce and colleagues have shown that these cytokines upregulate fatty acid oxidation and that this metabolic change plays a critical role in plasmacytoid dendritic cell activation and in anti-viral effects induced by type 1 IFNs.
  • Histone Deacetylase SIRT1 Negatively Regulates the Differentiation of Interleukin-9-Producing CD4+ T Cells

    • Yu Wang,
    • Yujing Bi,
    • Xi Chen,
    • Chunxiao Li,
    • Yan Li,
    • Zhengguo Zhang,
    • Jian Wang,
    • Yun Lu,
    • Qing Yu,
    • Huilin Su,
    • Hui Yang,
    • Guangwei Liu
    Th9 cells are critical in controlling immune-associated diseases. Liu and colleagues demonstrate that histone deacetylase SIRT1 negatively regulates the activities of mTOR and HIF1α signaling, couples with glycolysis metabolism, suppresses IL-9 production of CD4+ T cells, alleviates allergic airway inflammation, and promotes cancerous tumor growth.
  • Store-Operated Ca2+ Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity

    • Martin Vaeth,
    • Miriam Eckstein,
    • Patrick J. Shaw,
    • Lina Kozhaya,
    • Jun Yang,
    • Friederike Berberich-Siebelt,
    • Robert Clancy,
    • Derya Unutmaz,
    • Stefan Feske
    Germinal center reactions are tightly regulated by follicular helper (Tfh) and regulatory (Tfr) T cells. Feske and colleagues demonstrate that both Tfh and Tfr cells critically depend on store-operated calcium entry (SOCE) to prevent autoimmunity and promote anti-viral immune responses.
  • Lipopolysaccharide-Induced CD300b Receptor Binding to Toll-like Receptor 4 Alters Signaling to Drive Cytokine Responses that Enhance Septic Shock

    • Oliver H. Voss,
    • Yousuke Murakami,
    • Mirna Y. Pena,
    • Ha-Na Lee,
    • Linjie Tian,
    • David H. Margulies,
    • Jonathan M. Street,
    • Peter S.T. Yuen,
    • Chen-Feng Qi,
    • Konrad Krzewski,
    • John E. Coligan
    Host defense against gram-negative bacteria is facilitated by LPS recognition by TLR4-expressing immune cells, primarily macrophages. Coligan and colleagues identify CD300b as an LPS binding receptor and show that during acute infection (septic shock), CD300b-TLR4 complex formation regulates both TLR4-MyD88- and TLR4-TRIF-meditated signaling responses in macrophages, thereby augmenting lethal inflammation.
  • Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

    • Jincun Zhao,
    • Jingxian Zhao,
    • Ashutosh K. Mangalam,
    • Rudragouda Channappanavar,
    • Craig Fett,
    • David K. Meyerholz,
    • Sudhakar Agnihothram,
    • Ralph S. Baric,
    • Chella S. David,
    • Stanley Perlman
    Zoonotic CoVs have emerged twice in the past 10 years and have caused severe human respiratory disease. Using an alphavirus vaccine vector, Perlman and colleagues show that intranasal vaccination induces airway memory CD4+ T cell responses that protect mice from lethal challenge and are cross-reactive to different CoVs.
  • Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk

    • Kara G. Lassen,
    • Craig I. McKenzie,
    • Muriel Mari,
    • Tatsuro Murano,
    • Jakob Begun,
    • Leigh A. Baxt,
    • Gautam Goel,
    • Eduardo J. Villablanca,
    • Szu-Yu Kuo,
    • Hailiang Huang,
    • Laurence Macia,
    • Atul K. Bhan,
    • Marcel Batten,
    • Mark J. Daly,
    • Fulvio Reggiori,
    • Charles R. Mackay,
    • Ramnik J. Xavier
    Gene mapping efforts have identified numerous disease-associated genes, but understanding how these genes influence disease has proved challenging. Xavier and colleagues identify a role for GPR65 in lysosomal homeostasis and demonstrate that the IBD-associated risk variant GPR65 I231L confers lysosomal dysfunction with effects on autophagy, pathogen clearance, and intestinal homeostasis.
  • Inflammasome-Dependent Induction of Adaptive NK Cell Memory

    • Jasper G. van den Boorn,
    • Christopher Jakobs,
    • Christian Hagen,
    • Marcel Renn,
    • Rosalie M. Luiten,
    • Cornelis J.M. Melief,
    • Thomas Tüting,
    • Natalio Garbi,
    • Gunther Hartmann,
    • Veit Hornung
    Natural killer cells can acquire properties that are consistent with features of immunological memory. Hornung and colleagues show that the contact-sensitizer monobenzone induces pigment cell-specific memory NK cells, while the NLRP3 inflammasome serves as a critical and non-redundant proinflammatory checkpoint in the formation of this memory NK cell response.
  • Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation

    • Yosuke Masamoto,
    • Shunya Arai,
    • Tomohiko Sato,
    • Akihide Yoshimi,
    • Naoto Kubota,
    • Iseki Takamoto,
    • Yoichiro Iwakura,
    • Akihiko Yoshimura,
    • Takashi Kadowaki,
    • Mineo Kurokawa
    Infection is a well-known complication of obesity. Kurokawa and colleagues demonstrated that adiponectin deficiency in obese bone marrow leads to inflammatory cytokine milieu characterized by high TNF and inhibits emergency granulopoiesis upon systemic bacterial infection, highlighting adiponectin as a legitimate target for obesity-related bacterial infections.
  • Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency

    • Asuka Terashima,
    • Kazuo Okamoto,
    • Tomoki Nakashima,
    • Shizuo Akira,
    • Koichi Ikuta,
    • Hiroshi Takayanagi
    Much has been done on the identification of HSC niche, but the role of osteoblasts in hematopoiesis is unknown in acute immune responses. Takayanagi and colleagues show that sepsis reduces the osteoblast number, which induces lymphopenia through IL-7 downregulation, demonstrating a reciprocal interaction between the immune and bone systems.
  • Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

    • Avery D. Posey Jr.,
    • Robert D. Schwab,
    • Alina C. Boesteanu,
    • Catharina Steentoft,
    • Ulla Mandel,
    • Boris Engels,
    • Jennifer D. Stone,
    • Thomas D. Madsen,
    • Karin Schreiber,
    • Kathleen M. Haines,
    • Alexandria P. Cogdill,
    • Taylor J. Chen,
    • Decheng Song,
    • John Scholler,
    • David M. Kranz,
    • Michael D. Feldman,
    • Regina Young,
    • Brian Keith,
    • Hans Schreiber,
    • Henrik Clausen,
    • Laura A. Johnson,
    • Carl H. June
    Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.
  • Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection

    • Marieke Pingen,
    • Steven R. Bryden,
    • Emilie Pondeville,
    • Esther Schnettler,
    • Alain Kohl,
    • Andres Merits,
    • John K. Fazakerley,
    • Gerard J. Graham,
    • Clive S. McKimmie
    The inoculation of viruses into mosquito bite sites is an important and common stage of arbovirus infections. McKimmie and colleagues show that inflammation at bite sites aids viral replication and dissemination in vivo, resulting in more severe infection. These findings define additional targets for post-exposure prophylactic intervention.

Correction

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