TY - JOUR
T1 - The ESX-5 secretion system of Mycobacterium marinum modulates the macrophage response
AU - Abdallah, A.M.
AU - Savage, N.D.
AU - van Zon, M.
AU - Wilson, L.
AU - Vandenbroucke-Grauls, C.M.J.E.
AU - van der Wel, N.N.
AU - Ottenhoff, TH
AU - Bitter, W.
AU - Ottenhoff, Tom H. M.
PY - 2008
Y1 - 2008
N2 - The ESX-5 secretion system of pathogenic mycobacteria is responsible for the secretion of various PPE and PE-PGRS proteins. To better understand the role of ESX-5 effector proteins in virulence, we analyzed the interactions of Mycobacterium marinum ESX-5 mutant with human macrophages (M phi). Both wild-type bacteria and the ESX-5 mutant were internalized and the ESX-5 mutation did not affect the escape of mycobacteria from phagolysosomes into the cytosol, as was shown by electron microscopy. However, the ESX-5 mutation strongly effected expression of surface Ags and cytokine secretion. Whereas wild-type M. marinum actively suppressed the induction of appreciable levels of IL-12p40, TNF-alpha, and IL-6, infection with the ESX-5 mutant resulted in strongly induced production of these proinflammatory cytokines. By contrast, infection with M. marinum wild-type strain resulted in a significant induction of IL-1 beta production as compared with the ESX-5 mutant. These results show that ESX-5 plays an essential role in the modulation of immune cytokine secretion by human M phi. Subsequently, we show that an intact ESX-5 secretion system actively suppresses TLR signaling-dependent innate immune cytokine secretion. Together, our results show that ESX-5 substrates, directly or indirectly, strongly modulate the human M phi response at various critical steps. The Journal of Immunology, 2008, 181: 7166-7175
AB - The ESX-5 secretion system of pathogenic mycobacteria is responsible for the secretion of various PPE and PE-PGRS proteins. To better understand the role of ESX-5 effector proteins in virulence, we analyzed the interactions of Mycobacterium marinum ESX-5 mutant with human macrophages (M phi). Both wild-type bacteria and the ESX-5 mutant were internalized and the ESX-5 mutation did not affect the escape of mycobacteria from phagolysosomes into the cytosol, as was shown by electron microscopy. However, the ESX-5 mutation strongly effected expression of surface Ags and cytokine secretion. Whereas wild-type M. marinum actively suppressed the induction of appreciable levels of IL-12p40, TNF-alpha, and IL-6, infection with the ESX-5 mutant resulted in strongly induced production of these proinflammatory cytokines. By contrast, infection with M. marinum wild-type strain resulted in a significant induction of IL-1 beta production as compared with the ESX-5 mutant. These results show that ESX-5 plays an essential role in the modulation of immune cytokine secretion by human M phi. Subsequently, we show that an intact ESX-5 secretion system actively suppresses TLR signaling-dependent innate immune cytokine secretion. Together, our results show that ESX-5 substrates, directly or indirectly, strongly modulate the human M phi response at various critical steps. The Journal of Immunology, 2008, 181: 7166-7175
U2 - https://doi.org/10.4049/jimmunol.181.10.7166
DO - https://doi.org/10.4049/jimmunol.181.10.7166
M3 - Article
C2 - 18981138
SN - 0022-1767
VL - 181
SP - 7166
EP - 7175
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -