Host defense responses to infection by Mycobacterium tuberculosis. Induction of IRF-1 and a serine protease inhibitor.
Alveolar macrophages and newly recruited monocytes are targets of infection by Mycobacterium tuberculosis. Therefore, we examined the expression of interferon regulatory factor 1 (IRF-1), which plays an important role in host defense against M. tuberculosis, in undifferentiated and differentiated cells. Infection induced IRF-1 in both. IRF-1 from undifferentiated, uninfected monocytic cell lines was modified during extraction to produce specific species that were apparently smaller than intact IRF-1. After infection by M. tuberculosis or differentiation, intact IRF-1 was recovered. Subcellular fractions were assayed for the ability to modify IRF-1 or inhibit its modification. A serine protease on the cytoplasmic surface of an organelle or vesicle in the "lysosomal/mitochondrial" fraction from undifferentiated cells was responsible for the modification of IRF-1. Thus, the simplest explanation of the modification is cleavage of IRF-1 by the serine protease. Recovery of intact IRF-1 correlated with induction of a serine protease inhibitor that was able to significantly reduce the modification of IRF-1. The inhibitor was present in the cytoplasm of M. tuberculosis-infected or -differentiated cells. It is likely that induction of both IRF-1 and the serine protease inhibitor in response to infection by M. tuberculosis represent host defense mechanisms.
Qiao
Yaming
Y
Public Health Research Institute, Newark, New Jersey 07103, USA.
Prabhakar
Savita
S
Coccia
Eliana M
EM
Weiden
Michael
M
Canova
Antony
A
Giacomini
Elena
E
Pine
Richard
R
D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D050856:Interferon Regulatory Factor-1; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013347:Subcellular Fractions
D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D015842:Serine Proteinase Inhibitors; D004247:DNA; D012697:Serine Endopeptidases