| Requirement for invariant chain in macrophages for Mycobacterium tuberculosis replication and CD1d antigen presentation. | |
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MedLine Citation:
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PMID: 21576321 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mycobacterium tuberculosis is an intracellular bacterium that persists in phagosomes of myeloid cells. M. tuberculosis-encoded factors support pathogen survival and reduce fusion of phagosomes with bactericidal lysosomal compartments. It is, however, not entirely understood if host factors that mediate endosomal fusion affect M. tuberculosis intracellular localization and survival. Neither is it known if endosomal fusion influences induction of host immune reactivity by M. tuberculosis-infected cells. Lysosomal degradation of M. tuberculosis appears to be pivotal for making available lipid substrates for assembly into lipid-CD1d complexes to allow activation of CD1d-restricted invariant natural killer T (iNKT) cells. To clarify the role for endosomal fusion in M. tuberculosis survival and induction of host CD1d-mediated immune defense, we focused our studies on the invariant chain (Ii). Ii regulates endosome docking and fusion and thereby controls endosomal transport. Through direct binding, Ii also directs intracellular transport of the class II major histocompatibility complex and CD1d. Our findings demonstrate that upon infection of Ii-knockout (Ii(-/-)) macrophages, M. tuberculosis is initially retained in early endosomal antigen 1-positive lysosomal-associated membrane protein 1-negative phagosomes, which results in slightly impaired pathogen replication. The absence of Ii did not affect the ability of uninfected and infected macrophages to produce nitric oxide, tumor necrosis factor alpha, or interleukin-12. However, induction of cell surface CD1d was impaired in infected Ii(-/-) macrophages, and CD1d-restricted iNKT cells were unable to suppress bacterial replication when they were cocultured with M. tuberculosis-infected Ii(-/-) macrophages. Thus, while the host factor Ii is not essential for the formation of the M. tuberculosis-containing vacuole, its presence is crucial for iNKT cell recognition of infected macrophages. |
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Authors:
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Fenna C M Sillé; Constance Martin; Pushpa Jayaraman; Alissa Rothchild; Sarah Fortune; Gurdyal S Besra; Samuel M Behar; Marianne Boes |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-05-16 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-18 Completed Date: 2011-09-13 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3053-63 Citation Subset: IM |
Affiliation:
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Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigen Presentation* Antigens, CD1d / immunology*, metabolism Antigens, Differentiation, B-Lymphocyte / genetics, immunology*, metabolism Endosomes / metabolism, microbiology Gene Deletion Histocompatibility Antigens Class II / genetics, immunology*, metabolism Interleukin-12 / metabolism Killer Cells, Natural / immunology Macrophages / immunology*, microbiology* Mice Mice, Inbred C57BL Mice, Knockout Microbial Viability Mycobacterium tuberculosis / immunology*, pathogenicity* Nitric Oxide / metabolism Tumor Necrosis Factor-alpha / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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5 R01 HL080330/HL/NHLBI NIH HHS; R01 HL080312/HL/NHLBI NIH HHS; R01-AR052810/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD1d; 0/Antigens, Differentiation, B-Lymphocyte; 0/Histocompatibility Antigens Class II; 0/Tumor Necrosis Factor-alpha; 0/invariant chain; 10102-43-9/Nitric Oxide; 187348-17-0/Interleukin-12 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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