PMID- 15258598
OWN - NLM
STAT- MEDLINE
DCOM- 20041014
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 84
IP  - 10
DP  - 2004 Oct
TI  - Chronic pneumonia despite adaptive immune response to Mycobacterium bovis BCG in 
      MyD88-deficient mice.
PG  - 1305-21
AB  - To assess the role of Toll-like receptor (TLR) signalling in host response to 
      mycobacterial infection, mice deficient in the TLR adaptor molecule myeloid 
      differentiation factor 88 (MyD88) were infected with the vaccine strain 
      Mycobacterium bovis (BCG), and the immune response and bacterial burden were 
      investigated. Macrophages and dendritic cells from MyD88-deficient mice 
      stimulated in vitro with BCG mycobacterial antigens produced very low levels of 
      proinflammatory cytokines, while the expression of costimulatory molecules such 
      as CD40 and CD86 was preserved. Upon systemic infection with BCG (2 x 10(6) CFU 
      i.v.) MyD88-deficient mice developed confluent chronic pneumonia with two log 
      higher CFU than wild-type mice. Interestingly, the infection was controlled in 
      liver and spleen and there was efficient systemic T-cell priming with high 
      IFNgamma production by CD4+ splenic T cells in MyD88-deficient mice. Lung 
      infiltrating cells showed IFNgamma production by pulmonary CD4+ T cells upon 
      specific restimulation, and a reduced capacity to produce nitric oxide and IL-10. 
      In summary, despite the dramatic reduction of the innate immune response, 
      MyD88-deficient mice were able to mount an efficient T-cell response to 
      mycobacterial antigens, which was however insufficient to control infection in 
      the lung, resulting in chronic pneumonia in MyD88-deficient mice.
FAU - Nicolle, Delphine M
AU  - Nicolle DM
AD  - Molecular Immunology and Embryology (IEM), CNRS, Orleans, France.
FAU - Pichon, Xavier
AU  - Pichon X
FAU - Bouchot, Andre
AU  - Bouchot A
FAU - Maillet, Isabelle
AU  - Maillet I
FAU - Erard, Francois
AU  - Erard F
FAU - Akira, Shizuo
AU  - Akira S
FAU - Ryffel, Bernhard
AU  - Ryffel B
FAU - Quesniaux, Valerie F J
AU  - Quesniaux VF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Cytokines)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Bacterial/immunology/pharmacology
MH  - Antigens, Differentiation/*physiology
MH  - CD4-Positive T-Lymphocytes/immunology/microbiology
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Dendritic Cells/immunology
MH  - Immunity, Active
MH  - Immunity, Innate
MH  - Macrophages/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mycobacterium bovis/*immunology
MH  - Myeloid Differentiation Factor 88
MH  - Pneumonia, Bacterial/*immunology/microbiology
MH  - Receptors, Immunologic/deficiency/*physiology
MH  - Tuberculosis/*immunology/microbiology
EDAT- 2004/07/20 05:00
MHDA- 2004/10/16 09:00
CRDT- 2004/07/20 05:00
PHST- 2004/07/20 05:00 [pubmed]
PHST- 2004/10/16 09:00 [medline]
PHST- 2004/07/20 05:00 [entrez]
AID - S0023-6837(22)60191-0 [pii]
AID - 10.1038/labinvest.3700149 [doi]
PST - ppublish
SO  - Lab Invest. 2004 Oct;84(10):1305-21. doi: 10.1038/labinvest.3700149.