Article
Virology
Michelli F. Oliveira, Alec Pankow, Thomas Vollbrecht, Nikesh M. Kumar, Gemma Cabalero, Caroline Ignacio, Mitchell Zhao, Andrej Vitomirov, Ben Gouaux, Masato Nakawawa, Ben Murrell, Ronald J. Ellis, Sara Gianella
Summary: Despite antiretroviral therapy (ART), HIV reservoirs persist in anatomic compartments, including the central nervous system (CNS) and lymphoid tissues. In this study, archival HIV DNA was characterized in the brains and peripheral lymphoid tissues of individuals with HIV who passed away while on ART. The study found evidence of HIV DNA in the majority of brain and all lymphoid tissues, with higher levels in lymphoid tissues compared to the brain. The study also observed differences in HIV reservoir levels between genders and identified intact HIV envelope sequences in most tissue reservoirs, suggesting the potential for viral replication. These findings contribute to our understanding of HIV persistence and inform future cure strategies.
JOURNAL OF VIROLOGY
(2023)
Article
Immunology
Matthew T. Ollerton, Joy M. Folkvord, Kristina K. Peachman, Soumya Shashikumar, Elaine B. Morrison, Linda L. Jagodzinski, Sheila A. Peel, Mohammad Khreiss, Richard T. D'Aquila, Sofia Casares, Mangala Rao, Elizabeth Connick
Summary: Humanized DRAGA mice can generate virus-specific antibodies in HIV-1 infection, but their support for germinal center responses is limited.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Jacqueline H. Y. Siu, Michael J. Pitcher, Thomas J. Tull, Rebekah L. Velounias, William Guesdon, Lucia Montorsi, Krishnaa T. Mahbubani, Richard Ellis, Pawan Dhami, Katrina Todd, Ulrich D. Kadolsky, Michelle Kleeman, David P. D'Cruz, Kourosh Saeb-Parsy, Mats Bemark, Gavin J. Pettigrew, Jo Spencer
Summary: This study provides a deep analysis of B cells in lymphoid tissues and blood of deceased organ donors, leading to the identification of two subsets of marginal zone B (MZB) cells with distinct features and roles in immune response and pathology, emphasizing the importance of considering MZB cell heterogeneity in studying human B cell responses.
SCIENCE IMMUNOLOGY
(2022)
Article
Infectious Diseases
Shetty Ravi Dyavar, Sushil Kumar, Nagsen Gautam, Anthony T. Podany, Lee C. Winchester, Jonathan A. Weinhold, Timothy M. Mykris, Palanisamy Nallasamy, Yazen Alnouti, Courtney Fletcher
Summary: The study found that changing the route of drug administration can impact drug uptake in different tissues. Intramuscular or subcutaneous administration can enhance the bioavailability of antiretroviral drugs in lymphatic tissues, which helps to limit viral persistence and eliminate viral sanctuaries in these tissues.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Allergy
Maryam Ghaedi, Fumio Takei
Summary: Innate lymphoid cells (ILCs) mainly reside at barrier surfaces and play a regulatory role in tissue homeostasis and immunity. They are divided into 3 groups based on similar effector programs to T cells, and their development from lymphoid progenitors in adult mouse bone marrow has been extensively studied.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Takahisa Yoshikawa, Akiko Oguchi, Naoya Toriu, Yuki Sato, Takashi Kobayashi, Osamu Ogawa, Hironori Haga, Satoko Sakurai, Takuya Yamamoto, Yasuhiro Murakawa, Motoko Yanagita
Summary: Ectopic lymphoid structures called tertiary lymphoid tissues (TLTs) develop in kidney diseases and worsen renal prognosis. Single-nucleus RNA sequencing and validation experiments reveal that TLTs amplify inflammation in injured kidneys by promoting proinflammatory phenotypes of surrounding cells. These findings shed light on TLT pathology and suggest potential therapeutic targets.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Biochemical Research Methods
Peter B. Jorgensen, Thomas M. Fenton, Urs M. Morbe, Lene B. Riis, Henrik L. Jakobsen, Ole H. Nielsen, William W. Agace
Summary: The authors present a protocol for isolating and studying human gut-associated lymphoid tissue, which allows identification and isolation of all human GALT and GALT-free intestinal lamina propria. This technique involves mechanical separation of intestinal mucosa from the submucosa to identify and isolate specific types of lymphoid tissue for downstream cellular and molecular characterization. The protocol, taking 4-10 hours, could be useful for researchers interested in intestinal immune development and function in health and disease.
Review
Immunology
Angela Boahen, Dailun Hu, Murray J. Adams, Philip K. Nicholls, Wayne K. Greene, Bin Ma
Summary: This review explores the connections between the central nervous system (CNS) and the peripheral nervous system (PNS) with the immune system, focusing on the impact of these interactions on health and disease. Understanding these neuroimmune interactions could lead to new therapeutic approaches for neurological, neuroimmunological, infectious, inflammatory, and immunological disorders.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Kai Yang
Summary: Regulatory T cells (Tregs) play important roles in immune regulation, and cellular metabolism is crucial for their function. Tregs reprogram cellular metabolic programs to sustain their suppressive function, and altered metabolism also influences Treg activation and function. Manipulation of systemic metabolites has emerged as an attractive strategy to modulate tissue Treg metabolism and improve treatment of immune-related diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Masaki Gomi, Yu Sakurai, Minami Sato, Hiroki Tanaka, Yumi Miyatake, Koichi Fujiwara, Mizuki Watanabe, Satoshi Shuto, Yuta Nakai, Kota Tange, Hiroto Hatakeyama, Hidetaka Akita
Summary: This study reports the development of a new lipid nanoparticle (LNP) that efficiently delivers messenger RNA (mRNA) to secondary lymphoid tissues. A microfluidic technique was used to incorporate alcohol-soluble phosphatidylserine (PS) derivatives, designed to target immune cells, into LNPs with high scalability and reproducibility. The resulting PS-loaded LNP delivered mRNA to the spleen more efficiently than a control LNP. Sub-organ analysis revealed extensive uptake of the PS-loaded LNP by tissue-resident macrophages in the red pulp and marginal zone of the spleen. Therefore, the PS-loaded LNP described in this study holds promise for clinical applications involving mRNA delivery to the spleen.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Immunology
Varun N. Kapoor, Soren Muller, Shilpa Keerthivasan, Markus Brown, Cecile Chalouni, Elaine E. Storm, Alessandra Castiglioni, Ryan Lane, Maximilian Nitschke, Claudia X. Dominguez, Jillian L. Astarita, Akshay T. Krishnamurty, Catherine B. Carbone, Yasin Senbabaoglu, Amber W. Wang, Xiumin Wu, Viviana Cremasco, Merone Roose-Girma, Lucinda Tam, Jonas Doerr, Mark Z. Chen, Wyne P. Lee, Zora Modrusan, Yeqing Angela Yang, Richard Bourgon, Wendy Sandoval, Andrey S. Shaw, Frederic J. de Sauvage, Ira Mellman, Christine Moussion, Shannon J. Turley
Summary: Fibroblastic reticular cells, specifically the Grem1(+) subset, play a crucial role in supporting T cell immunity and maintaining the homeostasis of tissue-resident cDCs in lymph nodes. Single-cell RNA sequencing analyses in both human and mouse lymph nodes reveal the significance of Grem1(+) FRCs in regulating lymphocyte compartmentalization and innate and adaptive immunity.
Article
Biochemistry & Molecular Biology
Zhao Zhang, Wei Hong, Hang Ruan, Ying Jing, Shengli Li, Yaoming Liu, Jun Wang, Wenbo Li, Lixia Diao, Leng Han
Summary: This study characterized the landscape of eRNA expression in normal human tissues, identifying associations between eRNAs and traits such as gender, race, and age. A co-expression network was constructed to identify putative eRNA regulators and target genes across different tissues. The data portal HeRA provides a user-friendly platform for accessing and exploring eRNA expression profiles, trait-related associations, and co-expression networks.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Transplantation
Yuki Sato, Masaru Tamura, Motoko Yanagita
Summary: Tertiary lymphoid tissues (TLTs) are abnormal lymphoid tissues that develop at sites of chronic inflammation in nonlymphoid organs. They play important roles in disease severity, prognosis and therapy response. The study of TLTs in the kidney is limited, but recent findings suggest that aged kidneys can form multiple TLTs after injury, with resident fibroblasts playing a crucial role. Moreover, TLTs are suggested to have potential as markers for kidney injury/inflammation and as therapeutic targets.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Immunology
Hiroyuki Arai, Yuki Sato, Motoko Yanagita
Summary: Fibroblasts play important roles in maintaining tissue structure and homeostasis under physiological conditions, but their phenotypic alterations can lead to various pathological conditions. Recent research has shown that fibroblasts consist of heterogeneous subpopulations with both beneficial and detrimental effects in a context-dependent manner, particularly in the development of chronic kidney disease in the kidney.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Katja J. Jarick, Patrycja M. Topczewska, Manuel O. Jakob, Hiroshi Yano, Mohammad Arifuzzaman, Xuemei Gao, Sotiria Boulekou, Vladislava Stokic-Trtica, Pierre S. Leclere, Alexandra Preusser, Zoe A. Rompe, Anton Stamm, Amy M. Tsou, Coco Chu, Frederik R. Heinrich, Gabriela M. Guerra, Pawel Durek, Andranik Ivanov, Dieter Beule, Sofia Helfrich, Claudia U. Duerr, Anja A. Kuehl, Christina Stehle, Chiara Romagnani, Mir-Farzin Mashreghi, Andreas Diefenbach, David Artis, Christoph S. N. Klose
Summary: This article investigates the role of innate lymphoid cells (ILCs) in protective immunity. Using a mouse model specific to ILCs, researchers found that ILC2s have non-redundant functions during steady state and disease, and they interact with adaptive immune cells to organize the immune system.
Article
Cell Biology
Paul Lopez, Oluwaseun Ajibola, Amelie Pagliuzza, Romaniya Zayats, Wan Hon Koh, Alon Herschhorn, Nicolas Chomont, Thomas T. Murooka
Summary: The migration of T cells in 3D collagen matrix enhances HIV infection and integration. Migratory T cells are less sensitive to antiretroviral drugs and can freely migrate into regions with high HIV densities, resulting in high infection rates. These findings indicate that the environmental context of initial HIV-T cell encounters modulates HIV-1 entry and integration efficiencies.
Article
Immunology
David Lessard, Karine Dube, Martin Bilodeau, Patrick Keeler, Shari Margolese, Ron Rosenes, Liliya Sinyavskaya, Madeleine Durand, Erika Benko, Colin Kovacs, Charlotte Guerlotte, Wangari Tharao, Keresa Arnold, Renee Masching, Darien Taylor, Jose Sousa, Mario Ostrowski, Jeff Taylor, Andy Kaytes, Davey Smith, Sara Gianella, Nicolas Chomont, Jonathan B. Angel, Jean-Pierre Routy, Eric A. Cohen, Bertrand Lebouche, Cecilia T. Costiniuk
Summary: This study explores the willingness of older people with HIV (PWHIV) to participate in HIV cure research at the end of life. The results indicate that most participants are willing to participate in research autopsy, HIV biobanking, and hypothetical medical studies, mainly for altruistic purposes. However, a dialogue should be initiated to provide necessary information, address concerns, and accommodate their needs and preferences.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2022)
Article
Immunology
Isabelle Turcotte, Mohamed El-Far, Manel Sadouni, Carl Chartrand-Lefebvre, Ali Filali-Mouhim, Remi Fromentin, Annie Chamberland, Mohammad-Ali Jenabian, Jean-Guy Baril, Benoit Trottier, Rejean Thomas, Cecile L. Tremblay, Madeleine Durand, Nicolas Chomont, Canadian HIV Aging Cohort Study
Summary: People with HIV diagnosed with atherosclerotic plaques have higher levels of HIV DNA compared to those without plaques. In a prediction model with 27 traditional and HIV-related risk factors, measures of HIV DNA were found to be among the most important predictors of plaque formation.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Pierre Gantner, Supranee Buranapraditkun, Amelie Pagliuzza, Caroline Dufour, Marion Pardons, Julie L. Mitchell, Eugene Kroon, Carlo Sacdalan, Nicha Tulmethakaan, Suteeraporn Pinyakorn, Merlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich, Denise Hsu, Sandhya Vasan, Lydie Trautmann, Remi Fromentin, Nicolas Chomont
Summary: During early stages of HIV infection, the virus initially targets a small population of proliferating memory CD4+ T cells with high surface expression of CCR5. Productively infected cells exhibit different phenotypes and TCR sequences depending on the stage of infection and location within the body. The TCR repertoire of infected cells is biased towards previously expanded and disseminated clones, suggesting independent infection events. Latent genetically intact proviruses are present early in infection, indicating simultaneous generation of latent infected cells.
Article
Virology
Christina Mallarino-Haeger, Maria Pino, Elise G. Viox, Amelie Pagliuzza, Colin T. King, Kevin Nguyen, Justin L. Harper, Sol del Mar Aldrete, Barbara Cervasi, Keith A. Delman, Michael C. Lowe, Nicolas Chomont, Vincent C. Marconi, Mirko Paiardini
Summary: Understanding the contributions of different T-cell subsets to the persistence and localization of the HIV reservoir is crucial for developing cure interventions. This study compared the levels of T-cell activation and the size of the HIV reservoir in blood, rectal tissue, and lymph nodes, and found that certain T-cell subsets had higher levels of HIV DNA and immune activation in lymph nodes compared to blood.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Caroline Dufour, Corentin Richard, Marion Pardons, Marta Massanella, Antoine Ackaoui, Ben Murrell, Bertrand Routy, Rejean Thomas, Jean-Pierre Routy, Remi Fromentin, Nicolas Chomont
Summary: The phenotypic diversity of HIV-infected cells persisting during antiretroviral therapies (ART) was investigated. CD4+ T cells expressing integrin VLA-4 were found to be enriched in replication-competent HIV. Clonally expanded cells with identical proviruses displayed diverse phenotypes, indicating the role of cellular proliferation in the phenotypic diversification of the HIV reservoir. Genetically intact and inducible viral genomes were associated with higher levels of VLA-4 expression in CD4+ T cells. Replication-competent HIV was highly enriched in memory CD4+ T cells expressing high levels of VLA-4.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Chris Y. Y. Chiu, Maya D. D. Schou, James H. H. McMahon, Steven G. G. Deeks, Remi Fromentin, Nicolas Chomont, Michelle N. N. Wykes, Thomas A. A. Rasmussen, Sharon R. R. Lewin
Summary: The expression of immune checkpoint proteins is elevated in people with HIV, both on and off antiretroviral therapy (ART). Soluble immune checkpoint proteins and their ligands can be detected in plasma and may correlate with HIV reservoir size and T-cell function. Further investigation is needed to understand the role of these soluble proteins in the treatment and cure of HIV infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Mariela P. Cabral-Piccin, Laura Papagno, Xavier Lahaye, Federico Perdomo-Celis, Stevenn Volant, Eoghann White, Sian Llewellyn-Lacey, David A. Price, Nicolas Chomont, Nicolas Manel, Asier Saez-Cirion, Victor Appay
Summary: HIV-2 primes CD8+ T cells with potent antiviral functionality by activating the cGAS/STING pathway, resulting in enhanced immune control of HIV-1. The use of cGAMP or other STING agonists can enhance CD8+ T cell-mediated immune responses against HIV-1, providing a new direction for HIV-1 therapy.
Article
Microbiology
Mathieu Dube, Olivier Tastet, Caroline Dufour, Geremy Sannier, Nathalie Brassard, Gloria-Gabrielle Delgado, Amelie Pagliuzza, Corentin Richard, Manon Nayrac, Jean-Pierre Routy, Alexandre Prat, Jacob D. Estes, Remi Fromentin, Nicolas Chomont, Daniel E. Kaufmann
Summary: During suppressive antiretroviral therapy, spontaneous transcription and translation of HIV can persist, with p24(-)expressing cells evident in 39% of participants. Active reservoirs are enriched in central memory T cells and CCR6(-) and activation marker-expressing cells. The magnitude of the active reservoir positively correlates with HIV-specific CD4(+) and CD8(+) T cell responses and multiple HIV-specific T cell clusters.
CELL HOST & MICROBE
(2023)
Article
Microbiology
Hiroshi Takata, Julie L. Mitchell, Julian Pacheco, Amelie Pagliuzza, Suteeraporn Pinyakorn, Supranee Buranapraditkun, Carlo Sacdalan, Louise Leyre, Sam Nathanson, Juyeon C. Kakazu, Jintana Intasan, Peeriya Prueksakaew, Nitiya Chomchey, Nittaya Phanuphak, Mark de Souza, Elias K. Haddad, Morgane Rolland, Sodsai Tovanabutra, Sandhya Vasan, Denise C. Hsu, Nicolas Chomont, Lydie Trautmann
Summary: This study found that HIV-specific CD8+ T cell responses and HIV reservoir declined significantly after 2 years of antiretroviral therapy (ART). Sustained HIV-specific CD8+ T cell responses were associated with a greater reduction of integrated HIV provirus. However, the magnitude of CD8+ T cells specific for different HIV proteins positively correlated with the active reservoir size during ART. High HIV DNA levels were strongly associated with maintenance of short-lived HIV-specific CD8+ T cells regardless of the time of ART initiation.
CELL HOST & MICROBE
(2023)
Article
Cell Biology
Caroline Dufour, Maria Julia Ruiz, Amelie Pagliuzza, Corentin Richard, Aniqa Shahid, Remi Fromentin, Rosalie Ponte, Amelie Cattin, Tomas Raul Wiche Salinas, Syim Salahuddin, Teslin Sandstrom, Stephanie Burke Schinkel, Cecilia T. Costiniuk, Mohammad-Ali Jenabian, Petronela Ancuta, Jean-Pierre Routy, Eric A. Cohen, Zabrina L. Brumme, Christopher Power, Jonathan B. Angel, Nicolas Chomont
Summary: HIV persists in various tissues during antiretroviral therapy, with different anatomical compartments contributing differently to the viral reservoir. In two individuals on suppressive ART, HIV DNA was found in all tissues, with significant variations across compartments. Intact HIV genomes were mainly detected in secondary lymphoid organs, indicating the potential migration and circulation of infected cells between anatomical sites.
Article
Microbiology
Olivia E. Harwood, Lea M. Matschke, Ryan V. Moriarty, Alexis J. Balgeman, Abigail J. Weaver, Amy L. Ellis-Connell, Andrea M. Weiler, Lee C. Winchester, Courtney V. Fletcher, Thomas C. Friedrich, Brandon F. Keele, David H. O'Connor, Jessica D. Lang, Matthew R. Reynolds, Shelby L. O'Connor
Summary: Persistent post-treatment control of HIV was observed in Mauritian cynomolgus macaques, indicating that small viral reservoirs and immune-mediated virus suppression play a role in this phenomenon. This model can help further understand the mechanisms behind post-treatment control and identify potential therapeutic targets for inducing durable HIV remission in humans.
Article
Cell Biology
Ralph-Sydney Mboumba Bouassa, Eve Comeau, Yulia Alexandrova, Amelie Pagliuzza, Alexis Yero, Suzanne Samarani, Judy Needham, Joel Singer, Terry Lee, Florian Bobeuf, Claude Vertzagias, Giada Sebastiani, Shari Margolese, Enrico Mandarino, Marina B. Klein, Bertrand Lebouche, Jean-Pierre Routy, Nicolas Chomont, Cecilia T. Costiniuk, Mohammad-Ali Jenabian
Summary: Chronic HIV infection is accompanied by persistent inflammation, and this study suggests that cannabinoids may help reduce systemic inflammation in people with HIV. The study found that oral cannabinoids, either in combination with THC and CBD or CBD-only, significantly reduced inflammatory markers and affected immune cell subsets. These findings can guide future large clinical trials investigating the anti-inflammatory properties of cannabinoids.
Article
Medicine, General & Internal
Lena Royston, Stephane Isnard, Carolina A. Berini, Simeng Bu, Peter L. Lakatos, Talat Bessissow, Nicolas Chomont, Marina Klein, Bertrand Lebouche, Alexandra de Pokomandy, Nadine Kronfli, Cecilia T. Costiniuk, Rejean Thomas, Cecile Tremblay, Guy Boivin, Jean-Pierre Routy
Summary: This study aims to assess whether letermovir, a novel anti-CMV drug, can inhibit CMV subclinical replication in HIV patients receiving ART, and subsequently reduce CMV-associated gut damage and inflammation. The study will conduct a 14-week open-label, randomized, controlled clinical trial with 60 CMV-seropositive ART-treated HIV patients. The effects of letermovir on gut damage, microbial translocation, inflammation, and HIV reservoir size will be evaluated.
Article
Immunology
Mehdi Benlarbi, Jonathan Richard, Catherine Bourassa, William D. Tolbert, Carl Chartrand-Lefebvre, Gabrielle Gendron-Lepage, Mohamed Sylla, Mohamed El-Far, Marc Messier-Peet, Camille Guertin, Isabelle Turcotte, Remi Fromentin, Myriam Maude Verly, Jeremie Prevost, Andrew Clark, Walther Mothes, Daniel E. Kaufmann, Frank Maldarelli, Nicolas Chomont, Philippe Begin, Cecile Tremblay, Jean-Guy Baril, Benoit Trottier, Sylvie Trottier, Ralf Duerr, Marzena Pazgier, Madeleine Durand, Andres Finzi
Summary: This study found that soluble glycoprotein 120 (sgp120) and gp120-specific anti-cluster A antibodies are associated with immune dysfunction, chronic inflammation, and subclinical cardiovascular disease in HIV-infected individuals.
JOURNAL OF INFECTIOUS DISEASES
(2023)
