Immunology

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Article Immunology

Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling

Hongxu Xian, Kosuke Watari, Elsa Sanchez-Lopez, Joseph Offenberger, Janset Onyuru, Harini Sampath, Wei Ying, Hal M. Hoffman, Gerald S. Shadel, Michael Karin

Summary: In stressed mitochondria, oxidized mtDNA fragments are released and trigger inflammation. Understanding this process is important for the development of treatments for chronic inflammatory diseases.

IMMUNITY (2022)

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Review Immunology

SARS-COV-2 Variants: Differences and Potential of Immune Evasion

Sandro M. Hirabara, Tamires D. A. Serdan, Renata Gorjao, Laureane N. Masi, Tania C. Pithon-Curi, Dimas T. Covas, Rui Curi, Edison L. Durigon

Summary: This review addresses key issues regarding SARS-CoV-2 variants, including the characteristics of variants with mutations in the S gene, evasion of neutralizing antibodies, potential risks of new pandemic waves, and prospects for further research and actions to prevent or reduce the impact of new variants during the current COVID-19 pandemic.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2022)

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Article Immunology

The state of complement in COVID-19

Behdad Afzali, Marina Noris, Bart N. Lambrecht, Claudia Kemper

Summary: Hyperactivation of the complement system is implicated in the pathology of COVID-19, with potential therapeutic benefits through complement inhibition. Latest research progress suggests targeting complement components for treatment may be beneficial in mitigating excessive inflammation and thrombosis in severe COVID-19 cases.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Allergy

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial

Claus Bachert, Joseph K. Han, Martin Y. Desrosiers, Philippe Gevaert, Enrico Heffler, Claire Hopkins, Jody R. Tversky, Peter Barker, David Cohen, Claire Emson, Ubaldo J. Martin, Vivian H. Shih, Sofia Necander, James L. Kreindler, Maria Jison, Viktoria Werkstrom

Summary: This study assessed the efficacy and safety of benralizumab in treating CRSwNP. The results showed that benralizumab significantly improved NPS and nasal blockage score, and had significant improvement on difficulty with sense of smell score. Subgroup analyses suggested influences of comorbid asthma, number of NP surgeries, sex, body mass index, and baseline blood eosinophil count on treatment effects.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2022)

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Review Immunology

Monkeypox: disease epidemiology, host immunity and clinical interventions

Fok-Moon Lum, Anthony Torres-Ruesta, Matthew Z. Tay, Raymond T. P. Lin, David C. Lye, Laurent Renia, Lisa F. P. Ng

Summary: In this review, the clinical, epidemiological, and immunological aspects of monkeypox virus (MPXV) infections are examined, with a focus on host immunity mechanisms. The unique epidemiological and pathological characteristics of the current non-endemic outbreak of the virus are also considered, along with vaccines, therapeutics, and outstanding research questions.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Immunology

Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity

Kebria Hezaveh, Rahul S. Shinde, Andreas Kloetgen, Marie Jo Halaby, Sara Lamorte, M. Teresa Ciudad, Rene Quevedo, Luke Neufeld, Zhe Qi Liu, Robbie Jin, Barbara T. Grunwald, Elisabeth G. Foerster, Danica Chaharlangi, Mengdi Guo, Priya Makhijani, Xin Zhang, Trevor J. Pugh, Devanand M. Pinto, Ileana L. Co, Alison P. McGuigan, Gun Ho Jang, Rama Khokha, Pamela S. Ohashi, Grainne M. O'Kane, Steven Gallinger, William W. Navarre, Heather Maughan, Dana J. Philpott, David G. Brooks, Tracy L. McGaha

Summary: The study demonstrates the critical role of AhR in the function of tumor-associated macrophages (TAMs) in PDAC, showing that deletion of Ahr reduces PDAC growth, increases the frequency of IFN CD8(+) T cells, and dietary tryptophan metabolism affects AhR activity through the conversion of tryptophan to indoles by Lactobacillus. High AHR expression in PDAC patients is associated with disease progression, mortality, and an immune-suppressive TAM phenotype, indicating a conserved regulatory axis in human disease.

IMMUNITY (2022)

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Article Oncology

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET - a phase I, single-arm study

Ana Oaknin, Lucy Gilbert, Anna Tinker, Jubilee Brown, Cara Mathews, Joshua Press, Renaud Sabatier, David M. O'Malley, Vanessa Samouelian, Valentina Boni, Linda Duska, Sharad Ghamande, Prafull Ghatage, Rebecca Kristeleit, Charles Leath, Wei Guo, Ellie Im, Sybil Zildjian, Xinwei Han, Tao Duan, Jennifer Veneris, Bhavana Pothuri

Summary: Dostarlimab demonstrated durable antitumor activity in patients with endometrial cancer, with a manageable safety profile.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Immunology

Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

Pranita D. Tamma, Samuel L. Aitken, Robert A. Bonomo, Amy J. Mathers, David van Duin, Cornelius J. Clancy

Summary: This article provides updated guidance on the treatment of infections caused by ESBL-E, CRE, and DTR-P. aeruginosa. The guidance was developed by a panel of infectious diseases specialists and includes preferred and alternative treatment recommendations. The document emphasizes the importance of consulting with an infectious diseases specialist for the treatment of antimicrobial-resistant infections.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Respiratory Aerosols Emitted by Patients With Coronavirus Disease 2019 (COVID-19) While Breathing, Talking, and Singing

Kristen K. Coleman, Douglas Jie Wen Tay, Kai Sen Tan, Sean Wei Xiang Ong, The Son Than, Ming Hui Koh, Yi Qing Chin, Haziq Nasir, Tze Minn Mak, Justin Jang Hann Chu, Donald K. Milton, Vincent T. K. Chow, Paul Anantharajah Tambyah, Mark Chen, Kwok Wai Tham

Summary: The study found that fine aerosols generated during talking and singing contain more SARS-CoV-2 copies than coarse aerosols, potentially playing a key role in virus transmission. Patients in earlier stages of illness were more likely to emit detectable RNA, highlighting the importance of addressing fine aerosol exposure, especially in indoor settings. Challenges remain in isolating viable SARS-CoV-2 from respiratory aerosol samples, prompting the need for larger-scale studies on emerging variants.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients

Alana F. Ogata, Chi-An Cheng, Michael Desjardins, Yasmeen Senussi, Amy C. Sherman, Megan Powell, Lewis Novack, Salena Von, Xiaofang Li, Lindsey R. Baden, David R. Walt

Summary: The study found that most participants showed detectable levels of SARS-CoV-2 protein as early as day 1 after receiving the mRNA-1273 vaccine, and the clearance of detectable SARS-CoV-2 protein correlated with the production of immunoglobulin G (IgG) and immunoglobulin A (IgA).

CLINICAL INFECTIOUS DISEASES (2022)

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Review Immunology

Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity

Tianhao Duan, Yang Du, Changsheng Xing, Helen Y. Y. Wang, Rong-Fu Wang

Summary: This article provides a detailed overview of the innate immune system's defense mechanisms against pathogens, with a focus on the role of Toll-like receptors (TLRs) in immune responses. TLRs not only link innate immunity to adaptive immunity, but also directly regulate the function of T cells. In addition, the article discusses the critical role of TLR signaling in host defense against infectious diseases, autoimmune diseases, and cancer.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Immunology

The Impact of Coronavirus Disease 2019 (COVID-19) on Healthcare-Associated Infections

Meghan A. Baker, Kenneth E. Sands, Susan S. Huang, Ken Kleinman, Edward J. Septimus, Neha Varma, Jackie Blanchard, Russell E. Poland, Micaela H. Coady, Deborah S. Yokoe, Sarah Fraker, Allison Froman, Julia Moody, Laurel Goldin, Amanda Isaacs, Kacie Kleja, Kimberly M. Korwek, John Stelling, Adam Clark, Richard Platt, Jonathan B. Perlin

Summary: COVID-19 surges adversely impact healthcare-associated infection rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

The BNT162b2 mRNA Vaccine Elicits Robust Humoral and Cellular Immune Responses in People Living With Human Immunodeficiency Virus (HIV)

Bezawit A. Woldemeskel, Andrew H. Karaba, Caroline C. Garliss, Evan J. Beck, Kristy H. Wang, Oliver Laeyendecker, Andrea L. Cox, Joel N. Blankson

Summary: Past studies have shown that some vaccines do not elicit optimal responses in individuals living with HIV. However, this study demonstrates that the BNT162b2 vaccine induces robust immune responses in these patients comparable to those in healthy donors.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Jinyi Tang, Cong Zeng, Thomas M. Cox, Chaofan Li, Young Min Son, In Su Cheon, Yue Wu, Supriya Behl, Justin J. Taylor, Rana Chakaraborty, Aaron J. Johnson, Dante N. Shiavo, James P. Utz, Janani S. Reisenauer, David E. Midthun, John J. Mullon, Eric S. Edell, Mohamad G. Alameh, Larry Borish, William G. Teague, Mark H. Kaplan, Drew Weissman, Ryan Kern, Haitao Hu, Robert Vassallo, Shan-Lu Liu, Jie Sun

Summary: SARS-CoV-2 mRNA vaccination induces strong immune responses in the circulation, but its effectiveness in the respiratory tract, especially against variants of concern like Omicron, is still uncertain. This study found lower neutralizing antibody responses in the respiratory tract of vaccinated individuals compared to COVID-19 convalescents, despite robust antibody responses in the blood. Vaccination also induced circulating B and T cell immunity, but these responses were absent in the respiratory tract. Mouse immunization experiments showed that systemic mRNA vaccination alone resulted in weak respiratory mucosal neutralizing antibody responses, but combining it with mucosal adenovirus-S immunization produced strong neutralizing antibody responses against both the ancestral virus and the Omicron variant. Overall, this study suggests that current COVID-19 vaccines are highly effective against severe disease, but provide limited protection against breakthrough infections, particularly by the Omicron sublineage.

SCIENCE IMMUNOLOGY (2022)

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Article Immunology

The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant

Jan-Stephan F. Sanders, Frederike J. Bemelman, A. Lianne Messchendorp, Carla C. Baan, Debbie van Baarle, Rob van Binnendijk, Dimitri A. Diavatopoulos, Sophie C. Frolke, Daryl Geers, Corine H. GeurtsvanKessel, Gerco den Hartog, Marieke van der Heiden, Celine Imhof, Marcia M. L. Kho, Marion P. G. Koopmans, S. Reshwan K. Malahe, Wouter B. Mattheussens, Renate van der Molen, Djenolan van Mourik, Ester B. M. Remmerswaal, Nynke Rots, Priya Vart, Rory D. de Vries, Ron T. Gansevoort, Luuk B. Hilbrands, Marlies E. J. Reinders

Summary: In kidney patients, the immunogenicity, tolerability, and safety of COVID-19 vaccination vary. Kidney transplant recipients have a poor immune response, while patients with CKD G4/5 and those on dialysis have a comparable response to the control group. Dialysis patients and transplant recipients experience fewer adverse events after vaccination.

TRANSPLANTATION (2022)

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Review Immunology

The type I interferonopathies: 10 years on

Yanick J. Crow, Daniel B. Stetson

Summary: The term 'type I interferonopathy' was coined 10 years ago to describe rare genetic diseases caused by aberrant upregulation of type I interferon signaling. Viral nucleic acid detection is crucial for effective immune response, but failure in self versus non-self discrimination can lead to Mendelian inborn errors of immunity characterized by upregulation of type I interferon signaling.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Immunology

Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae

Zoe Swank, Yasmeen Senussi, Zachary Manickas-Hill, Xu G. Yu, Jonathan Z. Li, Galit Alter, David R. Walt

Summary: This study analyzed plasma samples from PASC and COVID-19 patients and found that spike protein of SARS-CoV-2 can be detected predominantly in PASC patients for up to 12 months.

CLINICAL INFECTIOUS DISEASES (2023)

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Article Immunology

Novel Canine Coronavirus Isolated from a Hospitalized Patient With Pneumonia in East Malaysia

Anastasia N. Vlasova, Annika Diaz, Debasu Damtie, Leshan Xiu, Teck-Hock Toh, Jeffrey Soon-Yit Lee, Linda J. Saif, Gregory C. Gray

Summary: This study identified a novel canine-feline recombinant alphacoronavirus isolated from a child with pneumonia, suggesting recent zoonotic transmission and emphasizing the public health threat of animal CoVs. Better surveillance is needed to monitor these viruses and their potential impact on human health.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination

Rahul K. Suryawanshi, Irene P. Chen, Tongcui Ma, Abdullah M. Syed, Noah Brazer, Prachi Saldhi, Camille R. Simoneau, Alison Ciling, Mir M. Khalid, Bharath Sreekumar, Pei-Yi Chen, G. Renuka Kumar, Mauricio Montano, Ronne Gascon, Chia-Lin Tsou, Miguel A. Garcia-Knight, Alicia Sotomayor-Gonzalez, Venice Servellita, Amelia Gliwa, Jenny Nguyen, Ines Silva, Bilal Milbes, Noah Kojima, Victoria Hess, Maria Shacreaw, Lauren Lopez, Matthew Brobeck, Fred Turner, Frank W. Soveg, Ashley F. George, Xiaohui Fang, Mazharul Maishan, Michael Matthay, Mary Kate Morris, Debra Wadford, Carl Hanson, Warner C. Greene, Raul Andino, Lee Spraggon, Nadia R. Roan, Charles Y. Chiu, Jennifer A. Doudna, Melanie Ott

Summary: This study shows that infection with the Omicron variant induces a limited immune response and may not provide broad protection against non-Omicron variants in unvaccinated individuals. However, Omicron breakthrough infections enhance pre-existing immunity elicited by vaccines. This has important implications for controlling the pandemic and the use of vaccines.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Immunology

Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine

Chunfeng Li, Audrey Lee, Lilit Grigoryan, Prabhu S. Arunachalam, Madeleine K. D. Scott, Meera Trisal, Florian Wimmers, Mrinmoy Sanyal, Payton A. Weidenbacher, Yupeng Feng, Julia Z. Adamska, Erika Valore, Yanli Wang, Rohit Verma, Noah Reis, Diane Dunham, Ruth O'Hara, Helen Park, Wei Luo, Alexander D. Gitlin, Peter Kim, Purvesh Khatri, Kari C. Nadeau, Bali Pulendran

Summary: The BNT162b2 mRNA vaccine stimulates potent antibody and antigen-specific T cell responses, as well as enhanced innate responses after secondary immunization. Circulating IFN-gamma is mainly produced by natural killer cells and CD8(+) T cells in the draining lymph nodes. The CD8(+) T cell response is dependent on type I interferon-dependent MDA5 signaling.

NATURE IMMUNOLOGY (2022)

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