Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis to block CD1 molecule expression and disable the function of dendritic cell derived from infected monocyte.
We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte differentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb-monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses.
Gagliardi
Maria Cristina
MC
Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299. 00161, Roma, Italy.
Lemassu
Anne
A
Teloni
Raffaela
R
Mariotti
Sabrina
S
Sargentini
Valeria
V
Pardini
Manuela
M
Daffé
Mamadou
M
Nisini
Roberto
R
D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002473:Cell Wall / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D005936:Glucans / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D018949:Antigens, CD1; D018122:B7-1 Antigen; D005936:Glucans; D016753:Interleukin-10; D018664:Interleukin-12