Mycobacterium tuberculosis directs T helper 2 cell differentiation by inducing interleukin-1β production in dendritic cells.
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), resides and replicates within phagocytes and persists in susceptible hosts by modulating protective innate immune responses. Furthermore, M. tuberculosis promotes T helper 2 (Th2) immune responses by altering the balance of T cell polarizing cytokines in infected cells. However, cytokines that regulate Th2 cell differentiation during TB infection remain unknown. Here we show that IL-1β, produced by phagocytes infected by virulent M. tuberculosis strain H37Rv, directs Th2 cell differentiation. In sharp contrast, the vaccine strain bacille Calmette-Guérin as well as RD-1 and ESAT-6 mutants of H37Rv failed to induce IL-1β and promote Th2 cell differentiation. Furthermore, ESAT-6 induced IL-1β production in dendritic cells (DCs), and CD4(+) T cells co-cultured with infected DCs differentiated into Th2 cells. Taken together, our findings indicate that IL-1β induced by RD-1/ESAT-6 plays an important role in the differentiation of Th2 cells, which in turn facilitates progression of TB by inhibiting host protective Th1 responses.
International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Ved Prakash
VP
Dwivedi
Debapriya
D
Bhattacharya
Samit
S
Chatterjee
Durbaka Vijay Raghva
DV
Prasad
Debprasad
D
Chattopadhyay
Luc
L
Van Kaer
William R
WR
Bishai
Gobardhan
G
Das
D000818:Animals; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000382:microbiology; D007107:Immune System; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010586:Phagocytes / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology* / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
D016207:Cytokines; D053583:Interleukin-1beta