Inhibition of cytokines expression in human microglia infected by virulent and non-virulent mycobacteria.
The pathogenesis of tuberculosis (TBC) meningitis is still unknown. As shown by previous studies, human microglia can be the target of mycobacteria, but no data are available about their cellular response to infection. Consequently, we studied the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-10 in human microglia pure cultures infected with the two variants of Mycobacterium avium (domed-opaque (SmD) and transparent (SmT)) and with Mycobacterium tuberculosis. Results showed that microglia was productively infected by mycobacteria which could grow inside the cells. Mycobacteria internalization was more rapid for M. avium, but M. tuberculosis infection turned out to be more efficient due to the incorporation of densely packed bacteria. TNF-alpha expression was not affected by M. avium, whereas an increase followed by a decrease was observed in M. tuberculosis. Both IL-1 and IL-10 cytokine expression was rapidly inhibited by infection with the more virulent bacteria, whereas the non-pathogenic one had almost no effect. Also, the expression of the co-stimulatory molecule CD137, a member of tumor necrosis factor receptor family, was affected by infection with virulent mycobacteria. Our results show that microglia response to mycobacterial infection is modulated in correlation with virulence, mainly toward inhibition of inflammatory response. This observation might be one of the mechanisms by which non-pathogenic mycobacteria are quickly eliminated, explaining one of the bases of virulence.
Curto
Monica
M
Department of Cytomorphology, School of Medicine, SS 554, Bivio Sestu, 09042 Monserrato (CA), Italy.
Reali
Camilla
C
Palmieri
Giuseppina
G
Scintu
Franca
F
Schivo
Maria Laura
ML
Sogos
Valeria
V
Marcialis
Maria Antonietta
MA
Ennas
Maria Grazia
MG
Schwarz
Herbert
H
Pozzi
Gianni
G
Gremo
Fulvia
F
D015703:Antigens, CD; D001483:Base Sequence; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017628:Microglia / Q000378:metabolism* / Q000382:microbiology; D009162:Mycobacterium avium / Q000472:pathogenicity / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014774:Virulence
D015703:Antigens, CD; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9