TY - JOUR
T1 - Mycobacteria clumping increase their capacity to damage macrophages
AU - Brambilla, Cecilia
AU - Llorens-Fons, Marta
AU - Julián, Esther
AU - Noguera-Ortega, Estela
AU - Tomàs-Martínez, Cristina
AU - Pérez-Trujillo, Miriam
AU - Byrd, Thomas F.
AU - Alcaide, Fernando
AU - Luquin, Marina
PY - 2016/10/4
Y1 - 2016/10/4
N2 - © 2016 Brambilla, Llorens-Fons, Julián, Noguera-Ortega, Tomàs-Martínez, Pérez-Trujillo, Byrd, Alcaide and Luquin. The rough morphotypes of non-tuberculous mycobacteria have been associated with the most severe illnesses in humans. This idea is consistent with the fact that Mycobacterium tuberculosis presents a stable rough morphotype. Unlike smooth morphotypes, the bacilli of rough morphotypes grow close together, leaving no spaces among them and forming large aggregates (clumps). Currently, the initial interaction of macrophages with clumps remains unclear. Thus, we infected J774 macrophages with bacterial suspensions of rough morphotypes of M. abscessus containing clumps and suspensions of smooth morphotypes, primarily containing isolated bacilli. Using confocal laser scanning microscopy and electron microscopy, we observed clumps of at least five rough-morphotype bacilli inside the phagocytic vesicles of macrophages at 3 h post-infection. These clumps grew within the phagocytic vesicles, killing 100% of the macrophages at 72 h post-infection, whereas the proliferation of macrophages infected with smooth morphotypes remained unaltered at 96 h post-infection. Thus, macrophages phagocytose large clumps, exceeding the bactericidal capacities of these cells. Furthermore, proinflammatory cytokines and granuloma-like structures were only produced by macrophages infected with rough morphotypes. Thus, the present study provides a foundation for further studies that consider mycobacterial clumps as virulence factors.
AB - © 2016 Brambilla, Llorens-Fons, Julián, Noguera-Ortega, Tomàs-Martínez, Pérez-Trujillo, Byrd, Alcaide and Luquin. The rough morphotypes of non-tuberculous mycobacteria have been associated with the most severe illnesses in humans. This idea is consistent with the fact that Mycobacterium tuberculosis presents a stable rough morphotype. Unlike smooth morphotypes, the bacilli of rough morphotypes grow close together, leaving no spaces among them and forming large aggregates (clumps). Currently, the initial interaction of macrophages with clumps remains unclear. Thus, we infected J774 macrophages with bacterial suspensions of rough morphotypes of M. abscessus containing clumps and suspensions of smooth morphotypes, primarily containing isolated bacilli. Using confocal laser scanning microscopy and electron microscopy, we observed clumps of at least five rough-morphotype bacilli inside the phagocytic vesicles of macrophages at 3 h post-infection. These clumps grew within the phagocytic vesicles, killing 100% of the macrophages at 72 h post-infection, whereas the proliferation of macrophages infected with smooth morphotypes remained unaltered at 96 h post-infection. Thus, macrophages phagocytose large clumps, exceeding the bactericidal capacities of these cells. Furthermore, proinflammatory cytokines and granuloma-like structures were only produced by macrophages infected with rough morphotypes. Thus, the present study provides a foundation for further studies that consider mycobacterial clumps as virulence factors.
KW - Clumps
KW - Cords
KW - Infection of macrophages
KW - Mycobacterium abscessus
KW - Rough morphotypes
KW - Smooth morphotypes
KW - Virulence factors
U2 - 10.3389/fmicb.2016.01562
DO - 10.3389/fmicb.2016.01562
M3 - Article
SN - 1664-302X
VL - 7
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 1562
ER -