Top 8 Biorxiv Papers Today in Immunology


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#1. Bacillus subtilis spore induces efficient generation of memory T cells via ICAM-1 expression on dendritic cells
Lulu Huang, Jian Lin, Yuchen Li, Penghao Zhang, Qinghua Yu, Qian Yang
The intestinal mucosa is the primary exposure and entry site of infectious organisms. Tissue-resident memory T cells (Trms) is an important first line of defense against infection in mucosal tissues, their function in intestinal immunization remains to be investigated. Here, we reported that the levels of local mucosal and systemic immune responses were enhanced through oral immunization with H9N2 whole inactivated virus (H9N2 WIV) plus spore. Subsequently, H9N2 WIV plus spore led to the generation of CD103 + CD69 + Trms, which was independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spore can stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, adipocyte supernatant or spore also upregulated intercellular adhesion molecule-1 (ICAM-1) expression on dendritic cells (DCs) ( P <0.01). Furthermore, the proportion of HA-tetramer + cells was severely curtailed when ICAM-1 expression was suppressed, which was also dependent on HA-loaded DCs. Taken together, our data...
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biorxivpreprint: Bacillus subtilis spore induces efficient generation of memory T cells via ICAM-1 expression on dendritic cells https://t.co/UAwrzKzyM8 #bioRxiv
biorxiv_immuno: Bacillus subtilis spore induces efficient generation of memory T cells via ICAM-1 expression on dendritic cells https://t.co/0xsA3ulBJI #biorxiv_immuno
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Authors: 6
Total Words: 0
Unqiue Words: 0

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#2. Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5
Angel K. Kongsomboonvech, Felipe Rodriguez, Anh L. Diep, Brandon M. Justice, Brayan E. Castallanos, Ana Camejo, Debanjan Mukhopadhyay, Gregory A. Taylor, Masahiro Yamamoto, Jeroen P.J. Saeij, Michael L. Reese, Kirk Jensen
Host resistance to Toxoplasma gondii relies on CD8 T cell IFNγ responses, which if modulated by the host or parasite could influence chronic infection and parasite transmission between hosts. Since host-parasite interactions that govern this response are not fully elucidated, we investigated requirements for eliciting naïve CD8 T cell IFNγ responses to a vacuolar resident antigen of T. gondii , TGD057. Naïve TGD057 antigen-specific CD8 T cells (T57) were isolated from transnuclear mice and responded to parasite-infected bone marrow-derived macrophages (BMDMs) in an antigen-dependent manner, first by producing IL-2 and then IFNγ. T57 IFNγ responses to TGD057 were independent of the parasite's protein export machinery ASP5 and MYR1. Instead, host immunity pathways downstream of the regulatory Immunity-Related GTPases (IRG), including partial dependence on Guanylate-Binding Proteins, are required. Multiple T. gondii ROP5 isoforms and allele types, including ‘avirulent’ ROP5A from clade A and D parasite strains, were able to suppress...
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biorxivpreprint: Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5 https://t.co/dFPICqH92U #bioRxiv
biorxiv_immuno: Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma ... https://t.co/FiBKMk4Mh8 #biorxiv_immuno
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Authors: 12
Total Words: 0
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#3. Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against an acute vaccinia infection in the lungs
Ning Yang, Joseph M. Luna, Peihong Dai, Yi Wang, Charles M. Rice, Liang Deng
The pulmonary immune system consists of a network of tissue-resident cells as well as immune cells that are recruited to the lungs during infection and/or inflammation. How the two immune components cross-talk during an acute viral infection is not well understood. Intranasal infection of mice with vaccinia virus causes lethal pneumonia and systemic dissemination. Here we report that vaccinia host range protein C7 is a critical virulence factor. Vaccinia virus with deletion of C7 (VACV∆C7L) is non-pathogenic in wild-type C57BL/6J mice, but it gains virulence in mice lacking STAT2, or IFNAR1, or MDA5/STING. We provide evidence that lung type II alveolar epithelial cells (AECs) provide first-line of defense against VACV∆C7L infection by inducing IFN-beta; and IFN-stimulated genes via the activation of the MDA5 and STING-mediated nucleic acid-sensing pathways. This leads to recruitment of CCR2+ inflammatory monocytes into the lungs to fight against viral dissemination.
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#4. Identification of novel, clinically correlated autoantigens in the monogenic autoimmune syndrome APS1 by PhIP-Seq
Sara E. Vazquez, Elise M.N. Ferre, David W. Scheel, Sara Sunshine, Brenda Miao, Caleigh Mandel-Brehm, Zoe Quandt, Alice Y. Chan, Mickie Cheng, Michael S. German, Michail S. Lionakis, Joseph L. DeRisi, Mark S. Anderson
The identification of autoantigens remains a critical challenge for understanding and treating autoimmune diseases. Autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic form of autoimmunity, presents as widespread autoimmunity with T and B cell responses to multiple organs. Importantly, autoantibody discovery in APS1 can illuminate fundamental disease pathogenesis, and many of the antigens found in APS1 extend to common autoimmune diseases. Here, we performed proteome-wide programmable phage-display (PhIP-Seq) on sera from an APS1 cohort and discovered multiple common antibody targets. These novel autoantigens exhibit tissue-restricted expression, including expression in enteroendocrine cells and dental enamel. Using detailed clinical phenotyping, we find novel associations between autoantibodies and organ-restricted autoimmunity, including between anti-KHDC3L autoantibodies and premature ovarian insufficiency, and between anti-RFX6 autoantibodies and diarrheal-type intestinal dysfunction. Our study highlights the...
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biorxivpreprint: Identification of novel, clinically correlated autoantigens in the monogenic autoimmune syndrome APS1 by PhIP-Seq https://t.co/VjbvAVRGu7 #bioRxiv
biorxiv_immuno: Identification of novel, clinically correlated autoantigens in the monogenic autoimmune syndrome APS1 by PhIP-Seq https://t.co/gbaUk3kIoW #biorxiv_immuno
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Authors: 13
Total Words: 0
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#5. Poor Quality Vβ Recombination Signal Sequences Enforce TCRβ Allelic Exclusion by Limiting the Frequency of Vβ Recombination
Glendon S Wu, Katherine S Yang-Iott, Morgann A Reed, Katharina E Hayer, Kyutae D Lee, Craig H Bassing
Monoallelic expression (allelic exclusion) of T and B lymphocyte antigen receptor genes is achieved by the assembly of a functional gene through V(D)J recombination on one allele and subsequent feedback inhibition of recombination on the other allele. There has been no validated mechanism for how only one allele of any antigen receptor locus assembles a functional gene prior to feedback inhibition. Here, we demonstrate that replacement of a single Vβ recombination signal sequence (RSS) with a better RSS increases Vβ rearrangement, reveals Tcrb alleles compete for utilization in the αβ T cell receptor (TCR) repertoire, and elevates the fraction of αβ T cells expressing TCRβ protein from both alleles. The data indicate that poor qualities of Vβ RSSs for recombination with Dβ and Jβ RSSs enforces allelic exclusion by stochastically limiting the incidence of functional Vβ rearrangements on both alleles before feedback inhibition terminates Vβ recombination.
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#6. Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma
Evgeniia Korotchenko, Victoria Schiessl, Sandra Scheiblhofer, Isabella Joubert, Helen Strandt, Theresa Neuper, Muamera Sarajlic, Renate Bauer, Mark Geppert, David Joedicke, Sabrina Wildner, Susanne Schaller, Stephan Winkler, Gabriele Gadermaier, Jutta Horejs-Hoeck, Richard Weiss
Background: Allergen-specific immunotherapy via the skin targets an area rich in antigen presenting cells, but can be associated with local and systemic side effect. Allergen-polysaccharide neoglycogonjugates can increase immunization efficacy by targeting and activating dendritic cells via C-type lectin receptors and reduce side effects. Objective: We investigated the immunogenicity, allergenicity and therapeutic efficacy of laminarin-ovalbumin neoglycoconjugates (LamOVA). Methods: The biological activity of LamOVA was characterized in vitro using bone marrow derived dendritic cells. Immunogenicity and therapeutic efficacy was analyzed in BALB/c mice. Epicutaneous immunotherapy (EPIT) was performed using fractional infrared laser ablation to generate micropores in the skin and the effects of LamOVA on blocking IgG, IgE, cellular composition of BAL, lung, and spleen, lung function, and T cell polarization was assessed. Results: Conjugation of laminarin to ovalbumin reduced its IgE binding capacity 5-fold and increased its...
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biorxivpreprint: Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma https://t.co/n0mutHVNhW #bioRxiv
biorxiv_immuno: Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and ... https://t.co/cntrx9OoEs #biorxiv_immuno
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Sample Sizes : [6, 12, 3, 6, 6, 5, 5, 12, 12]
Authors: 16
Total Words: 8536
Unqiue Words: 2552

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#7. Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
Alexander A Cohen, Zhi Yang, Priyanthi Gnanapragasam, Susan Ou, Kim-Marie Dam, Haoqing Wang, Pamela J Bjorkman
Current influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral immune response to conserved regions on influenza antigens are therefore required for recognition by broadly neutralizing antibodies. It has been suggested that B cells with receptors that recognize conserved epitopes would be preferentially stimulated through avidity effects by mosaic particles presenting multiple forms of a variable antigen. We adapted SpyCatcher-based platforms, AP205 virus-like particles (VLPs) and mi3 nanoparticles (NPs), to covalently co-display SpyTagged hemagglutinin (HA) trimers from different influenza strains. Here we show successful homotypic and heterotypic conjugation of up to 8 different HA trimers to both VLPs and NPs, and demonstrate that conjugated particles were stable for several weeks of storage. We characterized the HA-VLPs and HA-NPs by cryo-electron tomography to derive the average number of conjugated HAs and their separation distances, and compared...
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cryoEM_Papers: Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers https://t.co/KpYR3jqPVo
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Sample Sizes : [4]
Authors: 7
Total Words: 9492
Unqiue Words: 2976

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#8. T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species.
Alba Grifoni, Hannah Voic, Sandeep Kumar Dhanda, Conner K Kidd, James D Brien, Søren Buus, Anette Stryhn, Anna P. Durbin, Stephen Whitehead, Sean A. Diehl, Aruna Dharshan de Silva, Angel Balmaseda, Eva Harris, Daniela Weiskopf, Alessandro Sette
Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. Here, we tested pools of epitopes derived from dengue (DENV), zika (ZIKV), Japanese Encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by Intracellular Cytokine Staining (ICS)  using PBMCs of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccines. CD8 T cell responses recognized epitopes from multiple flaviviruses, however, the magnitude of cross-reactive responses was consistently several-fold lower than those to the autologous epitope pools, and associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing twenty-nine different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees...
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biorxivpreprint: T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species. https://t.co/Gc4PV554aW #bioRxiv
biorxiv_immuno: T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus ... https://t.co/phixldwe9I #biorxiv_immuno
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Sample Sizes : [8, 6, 15, 10]
Authors: 15
Total Words: 14842
Unqiue Words: 3988

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