Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88

Simple item page
dc.contributor.authorFremond, Cecile M
dc.contributor.authorYeremeev, Vladimir
dc.contributor.authorNicolle, Delphine M
dc.contributor.authorJacobs, Muazzam
dc.contributor.authorQuesniaux,Valerie F
dc.contributor.authorRyffel, Bernhard
dc.date.accessioned2017-11-01T08:12:00Z
dc.date.available2017-11-01T08:12:00Z
dc.date.issued2004
dc.date.updated2017-10-31T13:37:03Z
dc.description.abstractToll-like receptors (TLRs) such as TLR2 and TLR4 have been implicated in host response to mycobacterial infection. Here, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88) were infected with Mycobacterium tuberculosis (MTB). While primary MyD88–/– macrophages and DCs are defective in TNF, IL-12, and NO production in response to mycobacterial stimulation, the upregulation of costimulatory molecules CD40 and CD86 is unaffected. Aerogenic infection of MyD88–/– mice with MTB is lethal within 4 weeks with 2 log10 higher CFU in the lung; high pulmonary levels of cytokines and chemokines; and acute, necrotic pneumonia, despite a normal T cell response with IFN-γ production to mycobacterial antigens upon ex vivo restimulation. Vaccination with Mycobacterium bovis bacillus Calmette-Guérin conferred a substantial protection in MyD88–/– mice from acute MTB infection. These data demonstrate that MyD88 signaling is dispensable to raise an acquired immune response to MTB. Nonetheless, this acquired immune response is not sufficient to compensate for the profound innate immune defect and the inability of MyD88–/– mice to control MTB infection.
dc.identifierhttp://dx.doi.org/10.1172/JCI200421027
dc.identifier.apacitationFremond, C. M., Yeremeev, V., Nicolle, D. M., Jacobs, M., , & Ryffel, B. (2004). Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. <i>Journal of Clinical Investigation</i>, http://hdl.handle.net/11427/25982en_ZA
dc.identifier.chicagocitationFremond, Cecile M, Vladimir Yeremeev, Delphine M Nicolle, Muazzam Jacobs, , and Bernhard Ryffel "Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88." <i>Journal of Clinical Investigation</i> (2004) http://hdl.handle.net/11427/25982en_ZA
dc.identifier.citationFremond, C. M., Yeremeev, V., Nicolle, D. M., Jacobs, M., Quesniaux, V. F., & Ryffel, B. (2004). Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. Journal of Clinical Investigation, 114(12), 1790.
dc.identifier.ris TY - Journal Article AU - Fremond, Cecile M AU - Yeremeev, Vladimir AU - Nicolle, Delphine M AU - Jacobs, Muazzam AU - Quesniaux,Valerie F AU - Ryffel, Bernhard AB - Toll-like receptors (TLRs) such as TLR2 and TLR4 have been implicated in host response to mycobacterial infection. Here, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88) were infected with Mycobacterium tuberculosis (MTB). While primary MyD88–/– macrophages and DCs are defective in TNF, IL-12, and NO production in response to mycobacterial stimulation, the upregulation of costimulatory molecules CD40 and CD86 is unaffected. Aerogenic infection of MyD88–/– mice with MTB is lethal within 4 weeks with 2 log10 higher CFU in the lung; high pulmonary levels of cytokines and chemokines; and acute, necrotic pneumonia, despite a normal T cell response with IFN-γ production to mycobacterial antigens upon ex vivo restimulation. Vaccination with Mycobacterium bovis bacillus Calmette-Guérin conferred a substantial protection in MyD88–/– mice from acute MTB infection. These data demonstrate that MyD88 signaling is dispensable to raise an acquired immune response to MTB. Nonetheless, this acquired immune response is not sufficient to compensate for the profound innate immune defect and the inability of MyD88–/– mice to control MTB infection. DA - 2004 DB - OpenUCT DP - University of Cape Town J1 - Journal of Clinical Investigation LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 T1 - Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88 TI - Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88 UR - http://hdl.handle.net/11427/25982 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/25982
dc.identifier.vancouvercitationFremond CM, Yeremeev V, Nicolle DM, Jacobs M, , Ryffel B. Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. Journal of Clinical Investigation. 2004; http://hdl.handle.net/11427/25982.en_ZA
dc.language.isoeng
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.sourceJournal of Clinical Investigation
dc.source.urihttps://www.ncbi.nlm.nih.gov/pmc/journals/120/
dc.titleFatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Fremond_Mycobacterium_2004.pdf
Size:
1.22 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.72 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles