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dc.contributor.authorGideon, Hannah P.
dc.contributor.authorBehar, Samuel M
dc.contributor.authorShalek, Alex
dc.date2022-08-11T08:08:25.000
dc.date.accessioned2022-08-23T15:54:51Z
dc.date.available2022-08-23T15:54:51Z
dc.date.issued2020-10-26
dc.date.submitted2020-12-07
dc.identifier.citation<p>bioRxiv 2020.10.24.352492; doi: https://doi.org/10.1101/2020.10.24.352492. <a href="https://doi.org/10.1101/2020.10.24.352492" target="_blank" title="preprint on bioRxiv">Link to preprint on bioRxiv. </a></p>
dc.identifier.doi10.1101/2020.10.24.352492
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29632
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p> <p>Full author list omitted for brevity. For the full list of authors, see article. </p>
dc.description.abstractIn humans and nonhuman primates, Mycobacterium tuberculosis lung infection yields a complex multicellular structure—the tuberculosis granuloma. All granulomas are not equivalent, however, even within the same host: in some, local immune activity promotes bacterial clearance, while in others, it allows persistence or outgrowth. Here, we used single-cell RNA-sequencing to define holistically cellular responses associated with control in cynomolgus macaques. Granulomas that facilitated bacterial killing contained significantly higher proportions of CD4+ and CD8+ T cells expressing hybrid Type1-Type17 immune responses or stem-like features and CD8-enriched T cells with specific cytotoxic functions; failure to control correlated with mast cell, plasma cell and fibroblast abundance. Co-registering these data with serial PET-CT imaging suggests that a degree of early immune control can be achieved through cytotoxic activity, but that more robust restriction only arises after the priming of specific adaptive immune responses, defining new targets for vaccination and treatment.
dc.language.isoen_US
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectimmunology
dc.subjecttuberculosis
dc.subjectgranulomas
dc.subjectlymphocytes
dc.subjectBacterial Infections and Mycoses
dc.subjectBacteriology
dc.subjectImmunology and Infectious Disease
dc.subjectRespiratory Tract Diseases
dc.titleSingle-cell profiling of tuberculosis lung granulomas reveals functional lymphocyte signatures of bacterial control [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2860&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1849
dc.identifier.contextkey20463880
refterms.dateFOA2022-08-23T15:54:52Z
html.description.abstract<p><p id="x-x-x-p-4">In humans and nonhuman primates, <em>Mycobacterium tuberculosis</em> lung infection yields a complex multicellular structure—the tuberculosis granuloma. All granulomas are not equivalent, however, even within the same host: in some, local immune activity promotes bacterial clearance, while in others, it allows persistence or outgrowth. Here, we used single-cell RNA-sequencing to define holistically cellular responses associated with control in cynomolgus macaques. Granulomas that facilitated bacterial killing contained significantly higher proportions of <em>CD4+</em> and <em>CD8+</em> T cells expressing hybrid Type1-Type17 immune responses or stem-like features and <em>CD8</em>-enriched T cells with specific cytotoxic functions; failure to control correlated with mast cell, plasma cell and fibroblast abundance. Co-registering these data with serial PET-CT imaging suggests that a degree of early immune control can be achieved through cytotoxic activity, but that more robust restriction only arises after the priming of specific adaptive immune responses, defining new targets for vaccination and treatment.</p>
dc.identifier.submissionpathfaculty_pubs/1849
dc.contributor.departmentDepartment of Microbiology and Physiological Systems


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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.