المؤلفون: Montoya, Dennis J, Andrade, Priscila, Silva, Bruno JA, Teles, Rosane MB, Ma, Feiyang, Bryson, Bryan, Sadanand, Saheli, Noel, Teia, Lu, Jing, Sarno, Euzenir, Arnvig, Kristine B, Young, Douglas, Lahiri, Ramanuj, Williams, Diana L, Fortune, Sarah, Bloom, Barry R, Pellegrini, Matteo, Modlin, Robert L

المصدر: Cell Reports. 26(13)

مصطلحات موضوعية: Microbiology, Biological Sciences, Infectious Diseases, Genetics, Prevention, Emerging Infectious Diseases, Clinical Research, Vaccine Related, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Aetiology, Inflammatory and immune system, Infection, Good Health and Well Being, Adult, Antibodies, Bacterial, B-Cell Activating Factor, Female, Host-Pathogen Interactions, Humans, Immunity, Humoral, Interferon Type I, Leprosy, Male, Mycobacterium leprae, Plasma Cells, RNA, Bacterial, RNA, Messenger, RNA, Ribosomal, RNA-Seq, Transcriptome, bioinformatics, computational biology, heat shock, host-pathogen, humoral, immunology, microbiology, mycobacteria, plasma cell, sequencing, systems immunology, transcriptome, translational, tuberculosis, Biochemistry and Cell Biology, Medical Physiology, Biological sciences

الوصف: To understand how the interaction between an intracellular bacterium and the host immune system contributes to outcome at the site of infection, we studied leprosy, a disease that forms a clinical spectrum, in which progressive infection by the intracellular bacterium Mycobacterium leprae is characterized by the production of type I IFNs and antibody production. Dual RNA-seq on patient lesions identifies two independent molecular measures of M. leprae, each of which correlates with distinct aspects of the host immune response. The fraction of bacterial transcripts, reflecting bacterial burden, correlates with a host type I IFN gene signature, known to inhibit antimicrobial responses. Second, the bacterial mRNA:rRNA ratio, reflecting bacterial viability, links bacterial heat shock proteins with the BAFF-BCMA host antibody response pathway. Our findings provide a platform for the interrogation of host and pathogen transcriptomes at the site of infection, allowing insight into mechanisms of inflammation in human disease.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9sh6105vTest

المؤلفون: Sadanand, Saheli, Das, Jishnu, Chung, Amy W, Schoen, Matthew K, Lane, Sophie, Suscovich, Todd J, Streeck, Hendrik, Smith, Davey M, Little, Susan J, Lauffenburger, Douglas A, Richman, Douglas D, Alter, Galit

المصدر: AIDS. 32(4)

مصطلحات موضوعية: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Biotechnology, HIV/AIDS, Prevention, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Cohort Studies, Disease Progression, Disease Susceptibility, Early Diagnosis, HIV Antibodies, HIV Infections, Humans, Immunity, Cellular, Immunoglobulin G, env Gene Products, Human Immunodeficiency Virus, acute HIV, antibody-dependent effector functions, controllers, HIV-specific IgG, IgG subclasses, IgG2, IgG3, progressors, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences

الوصف: ObjectiveGiven the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between patients who ultimately became controllers versus those who became progressors.MethodsIgG was purified from plasma from nine acutely infected patients who subsequently controlled HIV spontaneously (controllers) and 10 acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 postinfection. Levels of clade B gp120-specific, gp140-specific and gp41-specific IgG antibody subclasses were measured. In addition, gp120-specific antibody-dependent cellular phagocytosis, rapid fluorescent antibody-dependent cellular cytotoxicity and antibody-dependent cellular viral inhibition were all assessed.ResultsAlthough no single antibody-related measurement was significantly associated with long-term HIV control, combinations of antibody-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 antibodies and losses in Env-specific IgG3 antibodies. Moreover, progressors, but not controllers, lost antibody-dependent cellular viral inhibition function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection.ConclusionThis study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.

الوصول الحر: https://escholarship.org/uc/item/521215kfTest

المؤلفون: Offersen, Rasmus, Yu, Wen-Han, Scully, Eileen P, Julg, Boris, Euler, Zelda, Sadanand, Saheli, Garcia-Dominguez, Dario, Zheng, Lu, Rasmussen, Thomas A, Jennewein, Madeleine F, Linde, Caitlyn, Sassic, Jessica, Lofano, Giuseppe, Vigano, Selena, Stephenson, Kathryn E, Fischinger, Stephanie, Suscovich, Todd J, Lichterfeld, Mathias, Lauffenburger, Douglas, Rosenberg, Erik S, Allen, Todd, Altfeld, Marcus, Charles, Richelle C, Østergaard, Lars, Tolstrup, Martin, Barouch, Dan H, Søgaard, Ole S, Alter, Galit

المساهمون: Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering

المصدر: Elsevier

الوصف: © 2020 The Authors Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.

وصف الملف: application/pdf

العلاقة: Cell Reports; https://hdl.handle.net/1721.1/136136Test

الإتاحة: https://hdl.handle.net/1721.1/136136Test

المؤلفون: Offersen, Rasmus, Yu, Wen-Han, Scully, Eileen P., Julg, Boris, Euler, Zelda, Sadanand, Saheli, Garcia-Dominguez, Dario, Zheng, Lu, Rasmussen, Thomas A., Jennewein, Madeleine F., Linde, Caitlyn, Sassic, Jessica, Lofano, Giuseppe, Vigano, Selena, Stephenson, Kathryn E., Fischinger, Stephanie, Suscovich, Todd J., Lichterfeld, Mathias, Lauffenburger, Douglas, Rosenberg, Erik S., Allen, Todd, Altfeld, Marcus, Charles, Richelle C., Østergaard, Lars, Tolstrup, Martin, Barouch, Dan H., Søgaard, Ole S., Alter, Galit

المساهمون: Massachusetts General Hospital

المصدر: Cell Reports ; volume 33, issue 11, page 108502 ; ISSN 2211-1247

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.celrep.2020.108502Test
https://api.elsevier.com/content/article/PII:S2211124720314911?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2211124720314911?httpAccept=text/plainTest

المؤلفون: Sadanand, Saheli, Schoen, Matthew K., Lane, Sophie, Streeck, Hendrik, Smith, Davey, Little, Susan, Richman, Douglas, Das, Jishnu, Chung, Amy H, Suscovich, Todd J, Lauffenburger, Douglas A, Alter, Galit

المساهمون: Massachusetts Institute of Technology. Anthropology Program, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Das, Jishnu, Chung, Amy H, Suscovich, Todd J, Lauffenburger, Douglas A, Alter, Galit

المصدر: PMC

الوصف: Objective: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-Associated features diverged in early HIV infection between patients who ultimately became controllers versus those who became progressors. Methods: IgG was purified from plasma from nine acutely infected patients who subsequently controlled HIV spontaneously (controllers) and 10 acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 postinfection. Levels of clade B gp120-specific, gp140-specific and gp41-specific IgG antibody subclasses were measured. In addition, gp120-specific antibody-dependent cellular phagocytosis, rapid fluorescent antibody-dependent cellular cytotoxicity and antibody-dependent cellular viral inhibition were all assessed. Results: Although no single antibody-related measurement was significantly associated with long-Term HIV control, combinations of antibody-Associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 antibodies and losses in Env-specific IgG3 antibodies. Moreover, progressors, but not controllers, lost antibody-dependent cellular viral inhibition function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. Conclusion: This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir. ; Massachusetts General ...

وصف الملف: application/pdf

العلاقة: http://dx.doi.org/10.1097/QAD.0000000000001716Test; AIDS; http://hdl.handle.net/1721.1/121022Test; Sadanand, Saheli, Jishnu Das, Amy W. Chung, Matthew K. Schoen, Sophie Lane, Todd J. Suscovich, Hendrik Streeck, et al. “Temporal Variation in HIV-Specific IgG Subclass Abs During Acute Infection Differentiates Spontaneous Controllers from Chronic Progressors.” AIDS (December 2017): 1.; orcid:0000-0002-0050-989X; orcid:0000-0003-1570-9445

الإتاحة: https://doi.org/10.1097/QAD.0000000000001716Test
http://hdl.handle.net/1721.1/121022Test

المؤلفون: Sadanand, Saheli

المصدر: Nature Medicine ; volume 25, issue 11, page 1647-1647 ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1038/s41591-019-0657-2Test
http://www.nature.com/articles/s41591-019-0657-2.pdfTest
http://www.nature.com/articles/s41591-019-0657-2Test

المؤلفون: Sadanand, Saheli

المصدر: Nature Biotechnology ; volume 37, issue 1, page 27-27 ; ISSN 1087-0156 1546-1696

مصطلحات موضوعية: Biomedical Engineering, Molecular Medicine, Applied Microbiology and Biotechnology, Bioengineering, Biotechnology

الإتاحة: https://doi.org/10.1038/nbt.4328Test
http://www.nature.com/articles/nbt.4328.pdfTest
http://www.nature.com/articles/nbt.4328Test

المؤلفون: Sadanand, Saheli

المصدر: Nature Biotechnology ; volume 36, issue 9, page 819-819 ; ISSN 1087-0156 1546-1696

مصطلحات موضوعية: Biomedical Engineering, Molecular Medicine, Applied Microbiology and Biotechnology, Bioengineering, Biotechnology

الإتاحة: https://doi.org/10.1038/nbt.4247Test
http://www.nature.com/articles/nbt.4247.pdfTest
http://www.nature.com/articles/nbt.4247Test

المؤلفون: Sadanand, Saheli

المصدر: Nature Medicine ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1038/d41591-021-00010-yTest
http://www.nature.com/articles/d41591-021-00010-y.pdfTest
http://www.nature.com/articles/d41591-021-00010-yTest

المؤلفون: Sadanand, Saheli

المصدر: Nature Medicine ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1038/d41591-021-00022-8Test
http://www.nature.com/articles/d41591-021-00022-8.pdfTest
http://www.nature.com/articles/d41591-021-00022-8Test