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1. Beyond Low Earth Orbit: Biological Research, Artificial Intelligence, and Self-Driving Labs

Author

Sanders, Lauren M., Yang, Jason H., Scott, Ryan T., Qutub, Amina Ann, Martin, Hector Garcia, Berrios, Daniel C., Hastings, Jaden J. A., Rask, Jon, Mackintosh, Graham, Hoarfrost, Adrienne L., Chalk, Stuart, Kalantari, John, Khezeli, Kia, Antonsen, Erik L., Babdor, Joel, Barker, Richard, Baranzini, Sergio E., Beheshti, Afshin, Delgado-Aparicio, Guillermo M., Glicksberg, Benjamin S., Greene, Casey S., Haendel, Melissa, Hamid, Arif A., Heller, Philip, Jamieson, Daniel, Jarvis, Katelyn J., Komarova, Svetlana V., Komorowski, Matthieu, Kothiyal, Prachi, Mahabal, Ashish, Manor, Uri, Mason, Christopher E., Matar, Mona, Mias, George I., Miller, Jack, Myers Jr., Jerry G., Nelson, Charlotte, Oribello, Jonathan, Park, Seung-min, Parsons-Wingerter, Patricia, Prabhu, R. K., Reynolds, Robert J., Saravia-Butler, Amanda, Saria, Suchi, Sawyer, Aenor, Singh, Nitin Kumar, Soboczenski, Frank, Snyder, Michael, Soman, Karthik, Theriot, Corey A., Van Valen, David, Venkateswaran, Kasthuri, Warren, Liz, Worthey, Liz, Zitnik, Marinka, and Costes, Sylvain V.

Subjects
Quantitative Biology - Other Quantitative Biology, Computer Science - Machine Learning
Abstract

Space biology research aims to understand fundamental effects of spaceflight on organisms, develop foundational knowledge to support deep space exploration, and ultimately bioengineer spacecraft and habitats to stabilize the ecosystem of plants, crops, microbes, animals, and humans for sustained multi-planetary life. To advance these aims, the field leverages experiments, platforms, data, and model organisms from both spaceborne and ground-analog studies. As research is extended beyond low Earth orbit, experiments and platforms must be maximally autonomous, light, agile, and intelligent to expedite knowledge discovery. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration on artificial intelligence, machine learning, and modeling applications which offer key solutions toward these space biology challenges. In the next decade, the synthesis of artificial intelligence into the field of space biology will deepen the biological understanding of spaceflight effects, facilitate predictive modeling and analytics, support maximally autonomous and reproducible experiments, and efficiently manage spaceborne data and metadata, all with the goal to enable life to thrive in deep space., Comment: 28 pages, 4 figures

Published
2021

2. Beyond Low Earth Orbit: Biomonitoring, Artificial Intelligence, and Precision Space Health

Author

Scott, Ryan T., Antonsen, Erik L., Sanders, Lauren M., Hastings, Jaden J. A., Park, Seung-min, Mackintosh, Graham, Reynolds, Robert J., Hoarfrost, Adrienne L., Sawyer, Aenor, Greene, Casey S., Glicksberg, Benjamin S., Theriot, Corey A., Berrios, Daniel C., Miller, Jack, Babdor, Joel, Barker, Richard, Baranzini, Sergio E., Beheshti, Afshin, Chalk, Stuart, Delgado-Aparicio, Guillermo M., Haendel, Melissa, Hamid, Arif A., Heller, Philip, Jamieson, Daniel, Jarvis, Katelyn J., Kalantari, John, Khezeli, Kia, Komarova, Svetlana V., Komorowski, Matthieu, Kothiyal, Prachi, Mahabal, Ashish, Manor, Uri, Martin, Hector Garcia, Mason, Christopher E., Matar, Mona, Mias, George I., Myers, Jr., Jerry G., Nelson, Charlotte, Oribello, Jonathan, Parsons-Wingerter, Patricia, Prabhu, R. K., Qutub, Amina Ann, Rask, Jon, Saravia-Butler, Amanda, Saria, Suchi, Singh, Nitin Kumar, Soboczenski, Frank, Snyder, Michael, Soman, Karthik, Van Valen, David, Venkateswaran, Kasthuri, Warren, Liz, Worthey, Liz, Yang, Jason H., Zitnik, Marinka, and Costes, Sylvain V.

Subjects
Quantitative Biology - Other Quantitative Biology, Computer Science - Machine Learning
Abstract

Human space exploration beyond low Earth orbit will involve missions of significant distance and duration. To effectively mitigate myriad space health hazards, paradigm shifts in data and space health systems are necessary to enable Earth-independence, rather than Earth-reliance. Promising developments in the fields of artificial intelligence and machine learning for biology and health can address these needs. We propose an appropriately autonomous and intelligent Precision Space Health system that will monitor, aggregate, and assess biomedical statuses; analyze and predict personalized adverse health outcomes; adapt and respond to newly accumulated data; and provide preventive, actionable, and timely insights to individual deep space crew members and iterative decision support to their crew medical officer. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration, on future applications of artificial intelligence in space biology and health. In the next decade, biomonitoring technology, biomarker science, spacecraft hardware, intelligent software, and streamlined data management must mature and be woven together into a Precision Space Health system to enable humanity to thrive in deep space., Comment: 31 pages, 4 figures

Published
2021

3. Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients

Author

Ishiyama, Kenichi, Arakawa-Hoyt, Janice, Aguilar, Oscar A, Damm, Izabella, Towfighi, Parhom, Sigdel, Tara, Tamaki, Stanley, Babdor, Joel, Spitzer, Matthew H, Reed, Elaine F, Sarwal, Minnie M, Lanier, Lewis L, Ahn, Richard, Brook, Jenny, Bunnapradist, Suphamai, Datta, Nakul, Deng, Mario, Diamond, Don, Doung, Tin, Gadzhyan, Janette, Elashoff, David, Gjertson, David, Groysberg, Victoria, Hoffman, Alexander, Lum, Erik, Pickering, Harry, Qian, Zach, Ramirez, Michelle, Rossetti, Maura, Rychov, Dimitri, Schaenman, Joanna, Schroeder, Andrew, Sen, Subha, Sim, Danielle, Sirota, Marina, Vicenti, Flavio, and Yang, Otto

Subjects
Kidney Disease, Infectious Diseases, Transplantation, Organ Transplantation, Inflammatory and immune system, Adult, CD8-Positive T-Lymphocytes, Cell Separation, Cytomegalovirus, Cytomegalovirus Infections, Female, Flow Cytometry, Graft Rejection, Humans, Kidney Transplantation, Killer Cells, Natural, Kinetics, Lymphocyte Activation, Male, Middle Aged, NK Cell Lectin-Like Receptor Subfamily C, Single-Cell Analysis, Viremia, NK cell, renal transplantation, cytomegalovirus, mass cytometry, cytotoxic lymphocyte, CMV Systems Immunobiology Group
Abstract

Cytomegalovirus (CMV) infection is associated with graft rejection in renal transplantation. Memory-like natural killer (NK) cells expressing NKG2C and lacking FcεRIγ are established during CMV infection. Additionally, CD8+ T cells expressing NKG2C have been observed in some CMV-seropositive patients. However, in vivo kinetics detailing the development and differentiation of these lymphocyte subsets during CMV infection remain limited. Here, we interrogated the in vivo kinetics of lymphocytes in CMV-infected renal transplant patients using longitudinal samples compared with those of nonviremic (NV) patients. Recipient CMV-seropositive (R+) patients had preexisting memory-like NK cells (NKG2C+CD57+FcεRIγ-) at baseline, which decreased in the periphery immediately after transplantation in both viremic and NV patients. We identified a subset of prememory-like NK cells (NKG2C+CD57+FcεRIγlow-dim) that increased during viremia in R+ viremic patients. These cells showed a higher cytotoxic profile than preexisting memory-like NK cells with transient up-regulation of FcεRIγ and Ki67 expression at the acute phase, with the subsequent accumulation of new memory-like NK cells at later phases of viremia. Furthermore, cytotoxic NKG2C+CD8+ T cells and γδ T cells significantly increased in viremic patients but not in NV patients. These three different cytotoxic cells combinatorially responded to viremia, showing a relatively early response in R+ viremic patients compared with recipient CMV-seronegative viremic patients. All viremic patients, except one, overcame viremia and did not experience graft rejection. These data provide insights into the in vivo dynamics and interplay of cytotoxic lymphocytes responding to CMV viremia, which are potentially linked with control of CMV viremia to prevent graft rejection.

Published
2022

4. Biomonitoring and precision health in deep space supported by artificial intelligence

Author

Scott, Ryan T., Sanders, Lauren M., Antonsen, Erik L., Hastings, Jaden J. A., Park, Seung-min, Mackintosh, Graham, Reynolds, Robert J., Hoarfrost, Adrienne L., Sawyer, Aenor, Greene, Casey S., Glicksberg, Benjamin S., Theriot, Corey A., Berrios, Daniel C., Miller, Jack, Babdor, Joel, Barker, Richard, Baranzini, Sergio E., Beheshti, Afshin, Chalk, Stuart, Delgado-Aparicio, Guillermo M., Haendel, Melissa, Hamid, Arif A., Heller, Philip, Jamieson, Daniel, Jarvis, Katelyn J., Kalantari, John, Khezeli, Kia, Komarova, Svetlana V., Komorowski, Matthieu, Kothiyal, Prachi, Mahabal, Ashish, Manor, Uri, Garcia Martin, Hector, Mason, Christopher E., Matar, Mona, Mias, George I., Myers, Jr, Jerry G., Nelson, Charlotte, Oribello, Jonathan, Parsons-Wingerter, Patricia, Prabhu, R. K., Qutub, Amina Ann, Rask, Jon, Saravia-Butler, Amanda, Saria, Suchi, Singh, Nitin Kumar, Snyder, Michael, Soboczenski, Frank, Soman, Karthik, Van Valen, David, Venkateswaran, Kasthuri, Warren, Liz, Worthey, Liz, Yang, Jason H., Zitnik, Marinka, and Costes, Sylvain V.

Published
2023
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5. Biological research and self-driving labs in deep space supported by artificial intelligence

Author

Sanders, Lauren M., Scott, Ryan T., Yang, Jason H., Qutub, Amina Ann, Garcia Martin, Hector, Berrios, Daniel C., Hastings, Jaden J. A., Rask, Jon, Mackintosh, Graham, Hoarfrost, Adrienne L., Chalk, Stuart, Kalantari, John, Khezeli, Kia, Antonsen, Erik L., Babdor, Joel, Barker, Richard, Baranzini, Sergio E., Beheshti, Afshin, Delgado-Aparicio, Guillermo M., Glicksberg, Benjamin S., Greene, Casey S., Haendel, Melissa, Hamid, Arif A., Heller, Philip, Jamieson, Daniel, Jarvis, Katelyn J., Komarova, Svetlana V., Komorowski, Matthieu, Kothiyal, Prachi, Mahabal, Ashish, Manor, Uri, Mason, Christopher E., Matar, Mona, Mias, George I., Miller, Jack, Myers, Jr., Jerry G., Nelson, Charlotte, Oribello, Jonathan, Park, Seung-min, Parsons-Wingerter, Patricia, Prabhu, R. K., Reynolds, Robert J., Saravia-Butler, Amanda, Saria, Suchi, Sawyer, Aenor, Singh, Nitin Kumar, Snyder, Michael, Soboczenski, Frank, Soman, Karthik, Theriot, Corey A., Van Valen, David, Venkateswaran, Kasthuri, Warren, Liz, Worthey, Liz, Zitnik, Marinka, and Costes, Sylvain V.

Published
2023
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7. Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy

Author

Hartmann, Felix J, Babdor, Joel, Gherardini, Pier Federico, Amir, El-Ad D, Jones, Kyle, Sahaf, Bita, Marquez, Diana M, Krutzik, Peter, O’Donnell, Erika, Sigal, Natalia, Maecker, Holden T, Meyer, Everett, Spitzer, Matthew H, and Bendall, Sean C

Subjects
Biological Sciences, Immunization, Vaccine Related, Immunotherapy, 4.1 Discovery and preclinical testing of markers and technologies, Cancer, Inflammatory and immune system, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Biomarkers, Clinical Trials as Topic, Female, Graft vs Host Disease, Humans, Immunophenotyping, Male, Middle Aged, Monitoring, Immunologic, Neoplasms, Reference Standards, CyTOF, biomarker, bone marrow transplantation, cancer, immunotherapy, mass cytometry, monitoring, phenotyping, Phenotyping, Monitoring, Mass Cytometry, Biomarker, Bone Marrow Transplantation, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery.

Published
2019

8. Simvastatin induces human gut bacterial cell surface genes.

Author

Escalante, Veronica, Nayak, Renuka R., Noecker, Cecilia, Babdor, Joel, Spitzer, Matthew, Deutschbauer, Adam M., and Turnbaugh, Peter J.

Subjects
BACTERIAL cell surfaces, BACTERIAL cell membranes, BACTERIAL genetics, HUMAN microbiota, DRUG resistance in bacteria
Abstract

Drugs intended to target mammalian cells can have broad off‐target effects on the human gut microbiota with potential downstream consequences for drug efficacy and side effect profiles. Yet, despite a rich literature on antibiotic resistance, we still know very little about the mechanisms through which commensal bacteria evade non‐antibiotic drugs. Here, we focus on statins, one of the most prescribed drug types in the world and an essential tool in the prevention and treatment of high circulating cholesterol levels. Prior work in humans, mice, and cell culture support an off‐target effect of statins on human gut bacteria; however, the genetic determinants of statin sensitivity remain unknown. We confirmed that simvastatin inhibits the growth of diverse human gut bacterial strains grown in communities and in pure cultures. Drug sensitivity varied between phyla and was dose‐dependent. We selected two representative simvastatin‐sensitive species for more in‐depth analysis: Eggerthella lenta (phylum: Actinobacteriota) and Bacteroides thetaiotaomicron (phylum: Bacteroidota). Transcriptomics revealed that both bacterial species upregulate genes in response to simvastatin that alter the cell membrane, including fatty acid biogenesis (E. lenta) and drug efflux systems (B. thetaiotaomicron). Transposon mutagenesis identified a key efflux system in B. thetaiotaomicron that enables growth in the presence of statins. Taken together, these results emphasize the importance of the bacterial cell membrane in countering the off‐target effects of host‐targeted drugs. Continued mechanistic dissection of the various mechanisms through which the human gut microbiota evades drugs will be essential to understand and predict the effects of drug administration in human cohorts and the potential downstream consequences for health and disease. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation

Author

Weimershaus, Mirjana, Mauvais, François-Xavier, Saveanu, Loredana, Adiko, Cézaire, Babdor, Joël, Abramova, Anastasia, Montealegre, Sebastian, Lawand, Myriam, Evnouchidou, Irini, Huber, Katharina Julia, Chadt, Alexandra, Zwick, Markus, Vargas, Pablo, Dussiot, Michael, Lennon-Dumenil, Ana Maria, Brocker, Thomas, Al-Hasani, Hadi, and van Endert, Peter

Published
2018
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16. Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1

Author

Rossignol, Julien, primary, Belaid, Zakia, additional, Fouquet, Guillemette, additional, Guillem, Flavia, additional, Rignault, Rachel, additional, Milpied, Pierre, additional, Renand, Amédée, additional, Coman, Tereza, additional, D’Aveni, Maud, additional, Dussiot, Michael, additional, Colin, Elia, additional, Levy, Jonathan, additional, Carvalho, Caroline, additional, Goudin, Nicolas, additional, Cagnard, Nicolas, additional, Côté, Francine, additional, Babdor, Joel, additional, Bhukhai, Kanit, additional, Polivka, Laura, additional, Bigorgne, Amélie E., additional, Halse, Héloise, additional, Marabelle, Aurélien, additional, Mouraud, Séverine, additional, Lepelletier, Yves, additional, Maciel, Thiago T., additional, Rubio, Marie-Thérèse, additional, Heron, Delphine, additional, Robert, Caroline, additional, Girault, Isabelle, additional, Lebeherec, Doris, additional, Scoazec, Jean-Yves, additional, Moura, Ivan, additional, Condon, Louise, additional, Weimershaus, Mirjana, additional, Pages, Franck, additional, Davoust, Jean, additional, Gross, David, additional, and Hermine, Olivier, additional

Published
2022
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17. Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation

Author

Beaune, Gregory, Blanch-Mercader, Carles, Douezan, Stephane, Dumond, Julien, Gonzalez-Rodriguez, David, Cuvelier, Damien, Ondarçuhu, Thierry, Sens, Pierre, Dufour, Sylvie, Murrell, Michael, Charles-Orszag, Arthur, Tsai, Feng-Ching, Bonazzi, Daria, Manriquez, Valeria, Sachse, Martin, Mallet, Adeline, Salles, Audrey, Melican, Keira, Staneva, Ralitza, Bertin, Aurélie, Millien, Corinne, Goussard, Sylvie, Lafaye, Pierre, Shorte, Spencer, Piel, Matthieu, Krijnse-Locker, Jacomine, Brochard-Wyart, Françoise, Bassereau, Patricia, Duménil, Guillaume, Weimershaus, Mirjana, Mauvais, Francois-Xavier, Saveanu, Loredana, Adiko, Cézaire, Babdor, Joel, Abramova, Anastasia, Montealegre, Sebastian, Lawand, Myriam, Evnouchidou, Irini, Huber, Katharina Julia, Chadt, Alexandra, Zwick, Markus, Vargas, Pablo, Dussiot, Michaël, Lennon-Dumenil, Ana Maria, Brocker, Thomas, Al-Hasani, Hadi, Van Endert, Peter, National Institute for Materials Science (NIMS), Physico-Chimie-Curie (PCC), Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Pathogénèse des Infections vasculaires, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microscopie ultrastructurale (plate-forme), Institut Pasteur [Paris], Imagopole (CITECH), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Neuroscience, Karolinska Institutet [Stockholm], Institut Curie, SAFT [Bordeaux], Société des accumulateurs fixes et de traction (SAFT), Ingénierie des Anticorps (plate-forme) - Antibody Engineering (Platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Compartimentation et dynamique cellulaires (CDC), Microscopie ultrastructurale - Ultrapole (CITECH), Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité et cancer, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Endosome, Antigen presentation, Fc receptor, Kinesins, Endosomes, Receptors, Fc, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Microtubules, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Mice, Cross-Priming, Phagosomes, Animals, lcsh:QH301-705.5, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Phagosome, Innate immune system, biology, Chemistry, Histocompatibility Antigens Class I, Cross-presentation, Dendritic cell, Immunity, Innate, Cell biology, Toll-Like Receptor 4, Protein Transport, 030104 developmental biology, lcsh:Biology (General), rab GTP-Binding Proteins, biology.protein, Kinesin, Female
Abstract

Summary: Both cross-presentation of antigens by dendritic cells, a key pathway triggering T cell immunity and immune tolerance, and survival of several pathogens residing in intracellular vacuoles are intimately linked to delayed maturation of vesicles containing internalized antigens and microbes. However, how early endosome or phagosome identity is maintained is incompletely understood. We show that Toll-like receptor 4 (TLR4) and Fc receptor ligation induces interaction of the GTPase Rab14 with the kinesin KIF16b mediating plus-end-directed microtubule transport of endosomes. As a result, Rab14 recruitment to phagosomes delays their maturation and killing of an internalized pathogen. Enhancing anterograde transport by overexpressing Rab14, promoting the GTP-bound Rab14 state, or inhibiting retrograde transport upregulates cross-presentation. Conversely, reducing Rab14 expression, destabilizing Rab14 endosomes, and inhibiting anterograde microtubule transport by Kif16b knockdown compromise cross-presentation. Therefore, regulation of early endosome trafficking by innate immune signals is a critical parameter in cross-presentation by dendritic cells. : Weimershaus et al. identify a molecular complex that controls the intracellular trafficking along microtubules of antigens internalized by dendritic cells. They show that this trafficking is regulated by innate immune signals and regulates presentation of internalized antigens to T lymphocytes. Keywords: antigen presentation, cross-presentation, dendritic cell, MHC class I, endosome, small GTPase, kinesin, Rab14

Published
2018
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18. Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy

Author

Hartmann, Felix J., primary, Babdor, Joel, additional, Gherardini, Pier Federico, additional, Amir, El-Ad D., additional, Jones, Kyle, additional, Sahaf, Bita, additional, Marquez, Diana M., additional, Krutzik, Peter, additional, O’Donnell, Erika, additional, Sigal, Natalia, additional, Maecker, Holden T., additional, Meyer, Everett, additional, Spitzer, Matthew H., additional, and Bendall, Sean C., additional

Published
2018
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19. Human CD4- invariant NKT lymphocytes regulate graft versus host disease

Author

Coman, Tereza, primary, Rossignol, Julien, additional, D’Aveni, Maud, additional, Fabiani, Bettina, additional, Dussiot, Michael, additional, Rignault, Rachel, additional, Babdor, Joel, additional, Bouillé, Marie, additional, Herbelin, André, additional, Coté, Francine, additional, Moura, Ivan C., additional, Hermine, Olivier, additional, and Rubio, Marie-Thérèse, additional

Published
2018
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20. IRAP+ endosomes restrict TLR9 activation and signaling

Author

Babdor, Joel, primary, Descamps, Delphyne, additional, Adiko, Aimé Cézaire, additional, Tohmé, Mira, additional, Maschalidi, Sophia, additional, Evnouchidou, Irini, additional, Vasconcellos, Luiz Ricardo, additional, De Luca, Mariacristina, additional, Mauvais, Francois-Xavier, additional, Garfa-Traore, Meriem, additional, Brinkmann, Melanie M, additional, Chignard, Michel, additional, Manoury, Bénédicte, additional, and Saveanu, Loredana, additional

Published
2017
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21. Intracellular Transport Routes for MHC I and Their Relevance for Antigen Cross-Presentation

Author

Adiko, Aimé Cézaire, Babdor, Joel, Gutiérrez-Martínez, Enric, Guermonprez, Pierre, and Saveanu, Loredana

Subjects
MHC class I molecules, Immunology, tubular endosomes, chemical and pharmacologic phenomena, Review, dendritic cells, cross-presentation, endosomal recycling compartment
Abstract

Cross-presentation, in which exogenous antigens are presented via MHC I complexes, is involved both in the generation of anti-infectious and anti-tumoral cytotoxic CD8(+) T cells and in the maintenance of immune tolerance. While cross-presentation was described almost four decades ago and while it is now established that some dendritic cell (DC) subsets are better than others in processing and cross-presenting internalized antigens, the involved molecular mechanisms remain only partially understood. Some of the least explored molecular mechanisms in cross-presentation concern the origin of cross-presenting MHC I molecules and the cellular compartments where antigenic peptide loading occurs. This review focuses on MHC I molecules and their intracellular trafficking. We discuss the source of cross-presenting MHC I in DCs as well as the role of the endocytic pathway in their recycling from the cell surface. Next, we describe the importance of the TAP peptide transporter for delivering peptides to MHC I during cross-presentation. Finally, we highlight the impact of innate immunity mechanisms on specific antigen cross-presentation mechanisms in which TLR activation modulates MHC I trafficking and TAP localization.

Published
2015

23. IRAP+endosomes restrict TLR9 activation and signaling

Author

Babdor, Joel, Descamps, Delphyne, Adiko, Aimé Cézaire, Tohmé, Mira, Maschalidi, Sophia, Evnouchidou, Irini, Vasconcellos, Luiz Ricardo, De Luca, Mariacristina, Mauvais, Francois-Xavier, Garfa-Traore, Meriem, Brinkmann, Melanie M, Chignard, Michel, Manoury, Bénédicte, and Saveanu, Loredana

Abstract

The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP+endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP+endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection. IRAP stabilized CpG-containing endosomes by interacting with the actin-nucleation factor FHOD4, which slowed the trafficking of TLR9 toward lysosomes. Thus, endosomal retention of TLR9 via the interaction of IRAP with the actin cytoskeleton is a mechanism that prevents hyper-activation of TLR9 in DCs.

Published
2017
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