Poster Presenter
Foamy Macrophages from Tuberculous
Patients’ Granulomas Constitute a Nutrient-Rich Reservoir
for M. Tuberculosis Persistence, and a Very Useful Model
for TB Drug Screening
Frédéric Altare, Pascale Peyron, Julien Vaubourgeix,
Yannick Poquet, Florence Levillain, Catherine Botanch, Fabienne
Bardou, Mamadou Daffé, Jean-François Emile, Bruno
Marchou, Pere-Joan Cardona, Chantal de Chastellier
France
Tuberculosis is characterized by a tight interplay between Mycobacterium
tuberculosis and host cells within granulomas. These cellular
aggregates restrict bacterial spreading, but do not kill all the
bacilli, which can persist for years. In depth investigation of
M. tuberculosis interactions with granuloma-specific cell
populations are needed to gain insight into mycobacterial persistence,
and to better understand the physiopathology of the disease.
We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific
cell population characterized by its high lipid content, and studied
their interaction with the tubercle bacillus. Within in vitro
human granuloma, M. tuberculosis triggered the differentiation
of human monocyte-derived macrophages into FMs. In these cells,
mycobacteria no longer replicated and switched to a dormant non-replicative
state. Electron microscopy observation of M. tuberculosis-infected
FMs showed that the mycobacteria-containing phagosomes migrate towards
host cell lipid bodies, a process which culminates with the engulfment
of the bacillus into the lipid droplets and with the accumulation
of lipids within the microbe.
Altogether, our results suggest that these cells might constitute
a reservoir used by the tubercle bacillus for long-term persistence
within its human host, and could provide a relevant model for the
screening of new antimicrobials against non-replicating persistent
mycobacteria
References:
-Foamy macrophages from tuberculous patients' granulomas constitute
a nutrient-rich reservoir for M. tuberculosis persistence.
Peyron P, Vaubourgeix J, Poquet Y, Levillain F, Botanch C, Bardou
F, Daffé M, Emile JF, Marchou B, Cardona PJ, de Chastellier
C, Altare F. PLoS Pathog. 2008 Nov;4(11):e1000204.
- Foamy macrophages and the progression of
the human tuberculosis granuloma.
Russell DG, Cardona PJ, Kim MJ, Allain S, Altare F. Nat Immunol.
2009 Sep;10(9):943-8.
