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dc.contributor.authorRothchild, Alissa C.
dc.contributor.authorJayaraman, Pushpa
dc.contributor.authorNunes-Alves, Claudio
dc.contributor.authorBehar, Samuel M.
dc.date2022-08-11T08:08:30.000
dc.date.accessioned2022-08-23T15:57:26Z
dc.date.available2022-08-23T15:57:26Z
dc.date.issued2014-01-02
dc.date.submitted2014-10-20
dc.identifier.citationPLoS Pathog. 2014 Jan;10(1):e1003805. doi: 10.1371/journal.ppat.1003805. <a href="http://dx.doi.org/10.1371/journal.ppat.1003805">Link to article on publisher's site</a>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1003805
dc.identifier.pmid24391492
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30195
dc.description.abstractInvariant natural killer T (iNKT) cells are activated during infection, but how they limit microbial growth is unknown in most cases. We investigated how iNKT cells suppress intracellular Mycobacterium tuberculosis (Mtb) replication. When co-cultured with infected macrophages, iNKT cell activation, as measured by CD25 upregulation and IFNgamma production, was primarily driven by IL-12 and IL-18. In contrast, iNKT cell control of Mtb growth was CD1d-dependent, and did not require IL-12, IL-18, or IFNgamma. This demonstrated that conventional activation markers did not correlate with iNKT cell effector function during Mtb infection. iNKT cell control of Mtb replication was also independent of TNF and cell-mediated cytotoxicity. By dissociating cytokine-driven activation and CD1d-restricted effector function, we uncovered a novel mediator of iNKT cell antimicrobial activity: GM-CSF. iNKT cells produced GM-CSF in vitro and in vivo in a CD1d-dependent manner during Mtb infection, and GM-CSF was both necessary and sufficient to control Mtb growth. Here, we have identified GM-CSF production as a novel iNKT cell antimicrobial effector function and uncovered a potential role for GM-CSF in T cell immunity against Mtb.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24391492&dopt=Abstract">Link to Article in PubMed</a>
dc.rights© 2014 Rothchild et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBacteria
dc.subjectBacterial Infections and Mycoses
dc.subjectImmunopathology
dc.subjectPathogenic Microbiology
dc.titleiNKT cell production of GM-CSF controls Mycobacterium tuberculosis
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume10
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1440&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/441
dc.identifier.contextkey6251720
refterms.dateFOA2022-08-23T15:57:26Z
html.description.abstract<p>Invariant natural killer T (iNKT) cells are activated during infection, but how they limit microbial growth is unknown in most cases. We investigated how iNKT cells suppress intracellular Mycobacterium tuberculosis (Mtb) replication. When co-cultured with infected macrophages, iNKT cell activation, as measured by CD25 upregulation and IFNgamma production, was primarily driven by IL-12 and IL-18. In contrast, iNKT cell control of Mtb growth was CD1d-dependent, and did not require IL-12, IL-18, or IFNgamma. This demonstrated that conventional activation markers did not correlate with iNKT cell effector function during Mtb infection. iNKT cell control of Mtb replication was also independent of TNF and cell-mediated cytotoxicity. By dissociating cytokine-driven activation and CD1d-restricted effector function, we uncovered a novel mediator of iNKT cell antimicrobial activity: GM-CSF. iNKT cells produced GM-CSF in vitro and in vivo in a CD1d-dependent manner during Mtb infection, and GM-CSF was both necessary and sufficient to control Mtb growth. Here, we have identified GM-CSF production as a novel iNKT cell antimicrobial effector function and uncovered a potential role for GM-CSF in T cell immunity against Mtb.</p>
dc.identifier.submissionpathfaculty_pubs/441
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.source.pagese1003805


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© 2014 Rothchild et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as © 2014 Rothchild et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.