Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses
A mechanistic understanding of immune responses elicited by multivalent nanoparticle immunogens is lacking in higher mammals. Ols et al. show in non-human primates that humoral responses are modulated by interrelated aspects of nanoparticles: their size and valency. Nanoparticle size slowed lymphatic transport, and valency-dependent avidity improved recruitment of low-affinity B cells, increasing B cell clonotype diversity and neutralization breadth. (Source: Immunity)
Source: Immunity - September 8, 2023 Category: Allergy & Immunology Authors: Sebastian Ols, Klara Lenart, Rodrigo Arcoverde Cerveira, Marcos C. Miranda, Natalie Brunette, Jana Kochmann, Martin Corcoran, Rebecca Skotheim, Annika Philomin, Alberto Cagigi, Brooke Fiala, Samuel Wrenn, Jessica Marcandalli, Fredrika Hellgren, Elizabeth Tags: Article Source Type: research
The virus-induced cyclic dinucleotide 2 ′3′-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila
In the model organism Drosophila melanogaster, two cGAS-like receptors participate in antiviral host-defense. Cai et al. explore STING-dependent immunity in several Drosophila species and report that flies encode up to seven cGAS-like receptors, which can produce distinct cyclic dinucleotide signals in response to viral infection. (Source: Immunity)
Source: Immunity - September 1, 2023 Category: Allergy & Immunology Authors: Hua Cai, Lihua Li, Kailey M. Slavik, Jingxian Huang, Ting Yin, Xianlong Ai, L éna Hédelin, Gabrielle Haas, Zhangmin Xiang, Yunyun Yang, Xiaoyan Li, Yuqiang Chen, Ziming Wei, Huimin Deng, Di Chen, Renjie Jiao, Nelson Martins, Carine Meignin, Philip J. Kr Tags: Article Source Type: research
Genetic variants of phospholipase C- γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer’s disease
Human genetic studies implicate PLCG2 variants in Alzheimer ’s disease risk, but the mechanism is unclear. Tsai et al. identify a PLCG2 loss-of-function variant that confers increased AD risk and demonstrate that gain- and loss-of-function PLCG2 AD variants uniquely alter microglial transcriptomes and direct plaque-responsive phenotypes, which may inform strategies to induce neuroprotective microglial responses to attenuate AD pathology. (Source: Immunity)
Source: Immunity - September 1, 2023 Category: Allergy & Immunology Authors: Andy P. Tsai, Chuanpeng Dong, Peter Bor-Chian Lin, Adrian L. Oblak, Gonzalo Viana Di Prisco, Nian Wang, Nicole Hajicek, Adam J. Carr, Emma K. Lendy, Oliver Hahn, Micaiah Atkins, Aulden G. Foltz, Jheel Patel, Guixiang Xu, Miguel Moutinho, John Sondek, Qish Tags: Article Source Type: research
Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation
Chronic inflammation causes a high burden of disability and mortality worldwide. Vascular macrophages are key orchestrators of homeostasis and vice versa of chronic inflammation. Pekayvaz et al. show how mural cells (the contractile cells of the vessel wall) actively sustain the vascular macrophage niche and keep it in a functional state. (Source: Immunity)
Source: Immunity - August 30, 2023 Category: Allergy & Immunology Authors: Kami Pekayvaz, Christoph Gold, Parandis Hoseinpour, Anouk Engel, Alejandro Martinez-Navarro, Luke Eivers, Raffaele Coletti, Markus Joppich, Fl ávio Dionísio, Rainer Kaiser, Lukas Tomas, Aleksandar Janjic, Maximilian Knott, Fitsumbirhan Mehari, Vivien Po Tags: Article Source Type: research
Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis
Interaction between leukocyte PECAM and endothelial cell PECAM is known to initiate transendothelial migration (TEM), but how these interactions result in TEM is not known. Fu and Sullivan et al. show that physical tension across endothelial PECAM in a complex with VE-cadherin and VEGFR2 transduces this signal and, in doing so, demonstrates a role for VEGFR2 in TEM. (Source: Immunity)
Source: Immunity - August 28, 2023 Category: Allergy & Immunology Authors: Tao Fu, David P. Sullivan, Annette M. Gonzalez, Maureen E. Haynes, Prarthana J. Dalal, Nakisha S. Rutledge, Abigail L. Tierney, Julia A. Yescas, Evan W. Weber, William A. Muller Tags: Article Source Type: research
Lymphatic endothelial transcription factor Tbx1 promotes an immunosuppressive microenvironment to facilitate post-myocardial infarction repair
Myocardial infarction (MI)-induced autoimmunity is detrimental, but it is usually resolved after the heart heals. However, the mechanism is unclear. Wang et al. report that Tbx1 upregulation in lymphatic endothelial cells enforces an immunosuppressive microenvironment to inhibit autoreactive CD8+ T cell expansion and increase reparative macrophages to repair post-MI damage. (Source: Immunity)
Source: Immunity - August 24, 2023 Category: Allergy & Immunology Authors: Wenfeng Wang, Xiao Li, Xiaoning Ding, Shanshan Xiong, Zhenlei Hu, Xuan Lu, Kan Zhang, Heng Zhang, Qianwen Hu, Kaa Seng Lai, Zhongxiang Chen, Junjie Yang, Hejie Song, Ye Wang, Lu Wei, Zeyang Xia, Bin Zhou, Yulong He, Jun Pu, Xiao Liu, Rongqin Ke, Tao Wu, C Tags: Article Source Type: research
A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor α determines T cell activation and function
Nuclear retinoic acid receptor alpha (RAR α) regulates gene transcription upon the binding of retinoic acid (RA). Larange, Takazawa, Kakugawa, Thiault et al. identify an RARα isoform in the cytoplasm of T cells (cRARα) and reveal that cRARα binds the TCR-ZAP-70 complex, thereby regulating T cell proliferation and effector differentia tion. RA counteracts TCR-engaged RARα, resulting in suboptimal TCR activation but enhanced Treg cell differentiation. (Source: Immunity)
Source: Immunity - August 18, 2023 Category: Allergy & Immunology Authors: Alexandre Larange, Ikuo Takazawa, Kiyokazu Kakugawa, Nicolas Thiault, SooMun Ngoi, Meagan E. Olive, Hitoshi Iwaya, Laetitia Seguin, Ildefonso Vicente-Suarez, Stephane Becart, Greet Verstichel, Ann Balancio, Amnon Altman, John T. Chang, Ichiro Taniuchi, Bj Tags: Article Source Type: research
Human microglia maturation is underpinned by specific gene regulatory networks
Molecular mechanisms that drive human microglia diversity remain largely unknown. Han and Li et al. characterize transitions in the transcriptomes and epigenomes of human fetal and postnatal microglia, develop computational tools that predict underlying gene regulatory networks, and demonstrate that core features of these networks can be captured by iPSC-derived microglia. (Source: Immunity)
Source: Immunity - August 14, 2023 Category: Allergy & Immunology Authors: Claudia Z. Han, Rick Z. Li, Emily Hansen, Samantha Trescott, Bethany R. Fixsen, Celina T. Nguyen, Cristina M. Mora, Nathanael J. Spann, Hunter R. Bennett, Olivier Poirion, Justin Buchanan, Anna S. Warden, Bing Xia, Johannes C.M. Schlachetzki, Martina P. P Tags: Resource Source Type: research
CTLA-4 blockade induces a microglia-Th1 cell partnership that stimulates microglia phagocytosis and anti-tumor function in glioblastoma
Immunotherapies against glioblastoma exhibit limited efficacy. Chen et al. examine the impact of immunotherapy in mesenchymal glioblastomas and find that αCTLA-4 treatment promotes tumor suppression in a manner dependent on CD4+ T cells. Mechanistically, microglia serve as essential MHC-II antigen-presenting cells that sustain anti-tumor IFNγ+ CD4+ T cells, which in turn stimulate microglial phagocytic function via AXL-MER signaling. (Source: Immunity)
Source: Immunity - August 11, 2023 Category: Allergy & Immunology Authors: Dan Chen, Siva Karthik Varanasi, Toshiro Hara, Kacie Traina, Ming Sun, Bryan McDonald, Yagmur Farsakoglu, Josh Clanton, Shihao Xu, Lizmarie Garcia-Rivera, Thomas H. Mann, Victor Du, H. Kay Chung, Ziyan Xu, Victoria Tripple, Eduardo Casillas, Shixin Ma, Ca Tags: Article Source Type: research
Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection
West et al. demonstrate that CD4+ T cell-intrinsic arginase 1 paces the transition of Th1 cells from their induction to their contraction program via balancing glutamine vs. arginine usage. They further show that Th1 cells lacking arginase 1 retain full pathogen clearance capacity but cause less Th1-asso ciated tissue pathology. (Source: Immunity)
Source: Immunity - August 11, 2023 Category: Allergy & Immunology Authors: Erin E. West, Nicolas S. Merle, Marcin M. Kami ński, Gustavo Palacios, Dhaneshwar Kumar, Luopin Wang, Jack A. Bibby, Kirsten Overdahl, Alan K. Jarmusch, Simon Freeley, Duck-Yeon Lee, J. Will Thompson, Zu-Xi Yu, Naomi Taylor, Marc Sitbon, Douglas R. Green Tags: Article Source Type: research
CTLA-4 blockade induces CD4+ T cell IFNγ-driven microglial phagocytosis and anti-tumor function in glioblastoma
Immunotherapies against glioblastoma exhibit limited efficacy. Chen et al. examine the impact of immunotherapy in mesenchymal glioblastomas and find that αCTLA-4 treatment promotes tumor suppression in a manner dependent on CD4+ T cells. Mechanistically, microglia serve as essential MHC-II antigen-presenting cells that sustain anti-tumor IFNγ+ CD4+ T cells, which in turn stimulate microglial phagocytic function via AXL-MER signaling. (Source: Immunity)
Source: Immunity - August 11, 2023 Category: Allergy & Immunology Authors: Dan Chen, Siva Karthik Varanasi, Toshiro Hara, Kacie Traina, Ming Sun, Bryan McDonald, Yagmur Farsakoglu, Josh Clanton, Shihao Xu, Lizmarie Garcia-Rivera, Thomas H. Mann, Victor Du, H. Kay Chung, Ziyan Xu, Victoria Tripple, Eduardo Casillas, Shixin Ma, Ca Tags: Article Source Type: research
Lymph node sharing between pancreas, gut, and liver leads to immune crosstalk and regulation of pancreatic autoimmunity
Lymph nodes (LNs) are critical for surveilling the tissue they drain. How LNs integrate and respond to complex cues in the situation of LN sharing between organs is unknown. Brown and Komnick et al. discover that LN co-drainage between the pancreas, gut, and liver leads to immune crosstalk, impacting pancreatic autoimmunity. (Source: Immunity)
Source: Immunity - August 8, 2023 Category: Allergy & Immunology Authors: Hailey Brown, Macy R. Komnick, Pamela H. Brigleb, Terence S. Dermody, Daria Esterh ázy Tags: Article Source Type: research
SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals
How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains unclear. Sokal et al. show that SARS-CoV-2 Omicron BA.1 breakthrough infections induce late remodeling and maturation of the pre-existing memory B cell pool, with progressively improved MBC affinity and neutralization breadth but limited recruitment of BA.1-restricted naive B cells. (Source: Immunity)
Source: Immunity - August 4, 2023 Category: Allergy & Immunology Authors: Aur élien Sokal, Giovanna Barba-Spaeth, Lise Hunault, Ignacio Fernández, Matteo Broketa, Annalisa Meola, Slim Fourati, Imane Azzaoui, Alexis Vandenberghe, Pauline Lagouge-Roussey, Manon Broutin, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetit Tags: Article Source Type: research
Heavy-chain CDR3-engineered B cells facilitate in vivo evaluation of HIV-1 vaccine candidates
V2-glycan/apex broadly neutralizing antibodies (bnAbs) recognize a closed quaternary structure of the HIV-1 envelope glycoprotein. He, Ou et al. introduced HCDR3 regions of neutralizing antibodies targeting this epitope into a diverse repertoire of murine B cell receptors (BCRs). Upon vaccination, these edited B cells affinity matured and generated potent neutralizing sera, highlighting the potential of an HCDR3-focused vaccine approac h. (Source: Immunity)
Source: Immunity - August 1, 2023 Category: Allergy & Immunology Authors: Wenhui He, Tianling Ou, Nickolas Skamangas, Charles C. Bailey, Naomi Bronkema, Yan Guo, Yiming Yin, Valerie Kobzarenko, Xia Zhang, Andi Pan, Xin Liu, Jinge Xu, Lizhou Zhang, Ava E. Allwardt, Debasis Mitra, Brian Quinlan, Rogier W. Sanders, Hyeryun Choe, M Tags: Article Source Type: research
Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis
Early social deprivation induces synaptic and behavioral deficits by unknown mechanisms. Byun et al. reveal that stress hormones induce excessive excitatory synapse elimination via the astrocytic GR-MERTK pathway. Ablating GR-MERTK from astrocytes prevents the loss of excitatory synapses, abnormal neuronal firing, and behavioral symptoms in ESD mice, emphasizing the critical roles of astrocyt ic phagocytosis in brain physiology and animal behavior. (Source: Immunity)
Source: Immunity - July 31, 2023 Category: Allergy & Immunology Authors: Youkyeong Gloria Byun, Nam-Shik Kim, Gyuri Kim, Yi-Seon Jeon, Jong Bin Choi, Chan-Woo Park, Kyungdeok Kim, Hyunsoo Jang, Jinkyeong Kim, Eunjoon Kim, Yong-Mahn Han, Ki-Jun Yoon, Seung-Hee Lee, Won-Suk Chung Tags: Article Source Type: research
