An increase in expression of a Mycobacterium tuberculosis mycolyl transferase gene (fbpB) occurs early after infection of human monocytes.
Changes in the mRNA levels of two Mycobacterium tuberculosis genes (fbpB known as antigen 85B, and hspX known as Acr) were studied in infected human monocytes. Antigen 85B is an enzyme involved in cell wall biosynthesis and is also a major target of the immune response. Acr is a stress protein believed to be involved in the bacillary response to adverse conditions and in non-replicating persistence. During the first 24 h of intracellular infection, the intramonocyte 85B mRNA level increased 54-fold (P = 0.00001) and 14.6 times in comparison with the 16S ribosomal rRNA. In contrast, the Acr mRNA fell 14.3 times. Although monocyte cytokine production was very variable, the 24 h secretion of tumour necrosis factor (TNF)-alpha correlated with the 85B-16S RNA ratio at 24 h (r = 0.77, Pcorr < 0.01). Furthermore, the addition of exogenous TNF-alpha to cultures was associated with a twofold increase in the 85B-16S ratio and, conversely, neutralization of endogenous TNF-alpha reduced the ratio. As antigen 85B also induces TNF-alpha, the positive feedback implied by our findings suggests a previously unsuspected role for this protein in the immunopathogenesis of tuberculosis.
Wilkinson
R J
RJ
Division of Infectious Diseases, Case Western Reserve University, Biomedical Research Building, 10900 Euclid Avenue, Cleveland, OH 44106-4984, USA. robertjwilkinson@yahoo.com
DesJardin
L E
LE
Islam
N
N
Gibson
B M
BM
Kanost
R A
RA
Wilkinson
K A
KA
Poelman
D
D
Eisenach
K D
KD
Toossi
Z
Z
D000217:Acyltransferases; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D006801:Humans; D009000:Monocytes / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D012333:RNA, Messenger / Q000378:metabolism; D014376:Tuberculosis / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C118127:HspX protein, Mycobacterium tuberculosis; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis