A large-scale systematic survey reveals recurring molecular features of public antibody responses to SARS-CoV-2
Since the start of the COVID-19 pandemic, isolation of antibodies to SARS-CoV-2 spike protein has been a major research focus. Wang et al. analyzed ∼8,000 published human monoclonal antibodies to the spike protein and identified sequence and molecular features of public antibody responses to SARS-CoV-2. The results enable the construction of a sequence-based deep learning model to predict antibody specificity. (Source: Immunity)
Source: Immunity - March 24, 2022 Category: Allergy & Immunology Authors: Yiquan Wang, Meng Yuan, Huibin Lv, Jian Peng, Ian A. Wilson, Nicholas C. Wu Tags: Article Source Type: research

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine
Tuft cells play a critical role in immunity against parasite infection, but whether Tuft cells participate in bacterial eradication is presently unclear. Xiong et  al. reveal that Tuft-2 cells mediate immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites. (Source: Immunity)
Source: Immunity - March 22, 2022 Category: Allergy & Immunology Authors: Zhen Xiong, Xiaoxiao Zhu, Jingjing Geng, Yuwei Xu, Runyuan Wu, Cunzhen Li, Dongdong Fan, Xiwen Qin, Ying Du, Yong Tian, Zusen Fan Tags: Article Source Type: research

Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T  cell clones
Using single-cell ECCITE-seq, Collora et  al. profiled 267 HIV-1 RNA+ cells and 68 expanded HIV-1 RNA+ T cell clones from 215,458 CD4+ T cells. HIV-1 resides in GZMB+ cytotoxic Th1 effector memory CD4+ T cell clones that are large and persistent. HIV-1-infected cytotoxic CD4+ T cells may evade cytotoxic CD8+ T cell killing through Se prin B9 degradation of granzyme B. (Source: Immunity)
Source: Immunity - March 22, 2022 Category: Allergy & Immunology Authors: Jack A. Collora, Runxia Liu, Delia Pinto-Santini, Neal Ravindra, Carmela Ganoza, Javier R. Lama, Ricardo Alfaro, Jennifer Chiarella, Serena Spudich, Karam Mounzer, Pablo Tebas, Luis J. Montaner, David van Dijk, Ann Duerr, Ya-Chi Ho Tags: Article Source Type: research

Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer
Meylan et  al. show that tertiary lymphoid structures found in tumors are sites of generation of fully mature B cell immunity. Plasma cells disseminate into tumor beds, producing antibodies that bind to tumor cells and initiate their apoptosis, providing a mechanism to support cancer immunotherapies that mod ulate the tumor microenvironment. (Source: Immunity)
Source: Immunity - February 28, 2022 Category: Allergy & Immunology Authors: Maxime Meylan, Florent Petitprez, Etienne Becht, Antoine Bougo üin, Guilhem Pupier, Anne Calvez, Ilenia Giglioli, Virginie Verkarre, Guillaume Lacroix, Johanna Verneau, Chen-Ming Sun, Pierre Laurent-Puig, Yann-Alexandre Vano, Reza Elaïdi, Arnaud Méjean Tags: Article Source Type: research

Tfh-cell-derived interleukin 21 sustains effector CD8+ T  cell responses during chronic viral infection
CD4+ T  cell help via IL-21 production is critical to sustain CD8+ T cell responses during chronic viral infection, but whether a particular subset mediates this process remains unclear. Zander et al. identify heterogeneity among IL-21-producing CD4+ T cells during chronic infection and find that Tfh-d erived IL-21 promotes effector CD8+ T cell development and antiviral immunity. (Source: Immunity)
Source: Immunity - February 24, 2022 Category: Allergy & Immunology Authors: Ryan Zander, Moujtaba Y. Kasmani, Yao Chen, Paytsar Topchyan, Jian Shen, Shikan Zheng, Robert Burns, Jennifer Ingram, Can Cui, Nikhil Joshi, Joseph Craft, Allan Zajac, Weiguo Cui Tags: Article Source Type: research

Bacterial infection disrupts established germinal center reactions through monocyte recruitment and impaired metabolic adaptation
Bacterial infections can interfere with the generation of antibody-mediated immunity through inhibition of germinal center formation. Biram et  al. demonstrate that secondary infection by S. Typhimurium and systemic inflammation impose a metabolic shift that is not tolerated by germinal center B cells. This process involves the CCR2-dependent recruitment of IFNγ-driven Sca-1+ monocytes into lymphoid organs and TNFα functions. (Source: Immunity)
Source: Immunity - February 18, 2022 Category: Allergy & Immunology Authors: Adi Biram, Jingjing Liu, Hadas Hezroni, Natalia Davidzohn, Dominik Schmiedel, Eman Khatib-Massalha, Montaser Haddad, Amalie Grenov, Sacha Lebon, Tomer Meir Salame, Nili Dezorella, Dotan Hoffman, Paula Abou Karam, Moshe Biton, Tsvee Lapidot, Mats Bemark, R Tags: Article Source Type: research

Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells
The origin and lineage affiliation of plasmacytoid dendritic cells (pDCs) remain controversial. Feng et  al. show that pDCs originate from the same pool of bone marrow progenitors as conventional dendritic cells (cDCs) and are clonally related to the cDC1 subset of cDCs. (Source: Immunity)
Source: Immunity - February 17, 2022 Category: Allergy & Immunology Authors: Jue Feng, Joseph N. Pucella, Geunhyo Jang, Marcela Alc ántara-Hernández, Samik Upadhaya, Nicholas M. Adams, Alireza Khodadadi-Jamayran, Colleen M. Lau, Marlon Stoeckius, Stephanie Hao, Peter Smibert, Aristotelis Tsirigos, Juliana Idoyaga, Boris Reizis Tags: Article Source Type: research

“Are you gonna go my way?”—Decisions at the Tfh-B cell interface
The generation of memory B cells and plasma cells is complex and involves inputs from the microenvironment, notably from T follicular helper cells. In last month ’s issue of Immunity, Yeh et al. and Song et al. refine our understanding of the B cell intrinsic and extrinsic requirements to generate effective humoral immunity in response to foreign antigens. (Source: Immunity)
Source: Immunity - February 17, 2022 Category: Allergy & Immunology Authors: Stuart G. Tangye, Klaus Warnatz Tags: Preview Source Type: research

Interferon- β acts directly on T cells to prolong allograft survival by enhancing regulatory T cell induction through Foxp3 acetylation
The mechanism by which IFN β, a pro-inflammatory cytokine, mediates its paradoxical immunosuppressive effects in autoimmunity and chronic viral infections remains elusive. Fueyo-González et al. use a transplant model to show that IFNβ synergizes with CTLA-4 Ig to prolong allograft survival. Mechanistically, IFNβ directly promotes Treg cell induction via activation of STAT1 signaling and P300-dependent Foxp3 acetylation. (Source: Immunity)
Source: Immunity - February 10, 2022 Category: Allergy & Immunology Authors: Francisco Fueyo-Gonz ález, Mitchell McGinty, Mehek Ningoo, Lisa Anderson, Chiara Cantarelli, Andrea Angeletti, Markus Demir, Inés Llaudó, Carolina Purroy, Nada Marjanovic, David Heja, Stuart C. Sealfon, Peter S. Heeger, Paolo Cravedi, Miguel Fribourg Tags: Article Source Type: research

Interferon- γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway
IFN γ modulates TLR signaling in macrophages, but the mechanism behind how their combined actions enact cell death is unclear. Simpson and colleagues demonstrate that both inducible nitric oxide synthase (iNOS) and caspase-8 promote mitochondrial-driven cell death during IFNγ and TLR signaling and inc rease SARS-CoV-2 disease severity. (Source: Immunity)
Source: Immunity - February 8, 2022 Category: Allergy & Immunology Authors: Daniel S. Simpson, Jiyi Pang, Ashley Weir, Isabella Y. Kong, Melanie Fritsch, Maryam Rashidi, James P. Cooney, Kathryn C. Davidson, Mary Speir, Tirta M. Djajawi, Sebastian Hughes, Liana Mackiewicz, Merle Dayton, Holly Anderton, Marcel Doerflinger, Yexuan Tags: Article Source Type: research

Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers
Tbet+CD11c+ B cells arise during viral infection and accumulate in aging and in settings of autoimmunity. Song et  al. find that Tbet+CD11c+ B cells require interactions with T follicular helper cells but develop outside of germinal centers, forming instead a distinct memory subset at the splenic marginal zone that can substantially contribute to recall responses. (Source: Immunity)
Source: Immunity - January 27, 2022 Category: Allergy & Immunology Authors: Wenzhi Song, Olivia Q. Antao, Emily Condiff, Gina M. Sanchez, Irene Chernova, Krzysztof Zembrzuski, Holly Steach, Kira Rubtsova, Davide Angeletti, Alexander Lemenze, Brian J. Laidlaw, Joe Craft, Jason S. Weinstein Tags: Article Source Type: research

Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5hiPD-1hi T follicular helper cells
T follicular helper (Tfh) cells within the germinal center (GC) arbitrate antibody affinity maturation. Yeh et  al. utilize various models to distinguish GC-resident Tfh cells, showing that the previous phenotypic definition of GCTfh cells includes a large subset that does not enter GCs. These CD90hi Tfh cells have different developmental requirements and activities than the rarer GC-resident Tfh cells (CD9 0neg/lo), implying distinct functions. (Source: Immunity)
Source: Immunity - January 25, 2022 Category: Allergy & Immunology Authors: Chen-Hao Yeh, Joel Finney, Takaharu Okada, Tomohiro Kurosaki, Garnett Kelsoe Tags: Article Source Type: research

IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment
IL-17A is critical for maintaining intestinal integrity and may play a beneficial role in IBD, but the extent of its tissue-specific roles remains unclear. Lin et  al. show that IL-17A acts specifically on Lgr5+ intestinal stem cells to induce Atoh1 expression and promote differentiation into secretory cells. Furthermore, IL-17A protects against DSS-induced injury through ATOH1+ cell-mediated regeneration of Lgr5+ ISCs. (Source: Immunity)
Source: Immunity - January 25, 2022 Category: Allergy & Immunology Authors: Xun Lin, Stephen J. Gaudino, Kyung Ku Jang, Tej Bahadur, Ankita Singh, Anirban Banerjee, Michael Beaupre, Timothy Chu, Hoi Tong Wong, Chang-Kyung Kim, Cody Kempen, Jordan Axelrad, Huakang Huang, Saba Khalid, Vyom Shah, Onur Eskiocak, Olivia B. Parks, Arta Tags: Article Source Type: research

Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVD-19 respiratory disease
Many individuals recovering from acute SARS-CoV-2 infection suffer prolonged respiratory dysfunction for months to years after viral clearance. Vijayakumar, Boustani, Ogger, Papadaki et al. show that individuals with persistent symptoms 3-6 months after infection have an altered airway immune cell landscape and evidence of ongoing lung damage. Importantly, different immune cell types correlate with the severity of distinct aspects of ongoing respiratory disease. (Source: Immunity)
Source: Immunity - January 25, 2022 Category: Allergy & Immunology Authors: Bavithra Vijayakumar, Karim Boustani, Patricia P. Ogger, Artemis Papadaki, James Tonkin, Christopher M. Orton, Poonam Ghai, Kornelija Suveizdyte, Richard J. Hewitt, Sujal R. Desai, Anand Devaraj, Robert J. Snelgrove, Philip L. Molyneaux, Justin L. Garner, Tags: Article Source Type: research

Response to Are NKT cells a useful predictor of COVID-19 severity?
The purpose of our study was to identify immune signatures specific to the immune response against SARS-CoV-2 by subtracting the immune signatures against other pathogens across patients with severe pneumonia. In order to do so, and to specifically interrogate functional features such as cytokine expression and activation/exhaustion states, we generated very broad phenotyping panels that allow the characterization of blood leukocytes. In order to have an unbiased workflow, we did not specifically interrogate certain rare subpopulations of cells such as iNKT cells (defined by CD1d tetramers loaded  with α-galactosylcerami...
Source: Immunity - January 22, 2022 Category: Allergy & Immunology Authors: Stefanie Kreutmair, Burkhard Becher Tags: Letter Source Type: research