Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T Cells.
BACKGROUND
Although it is well recognized that CD4(+) T cells and T helper (Th) 1 cytokines are critical in the cell-mediated response to Mycobacterium tuberculosis, it is also clear that this immunity alone is not enough. Understanding the roles of other T cell subsets and cytokines is essential for vaccine design and clinical immunotherapy against tuberculosis (TB).


OBJECTIVE
To investigate the clinical significance and possible regulatory mechanism of Th17 responses in human TB.


METHODS
The frequencies of IFN-gamma-, IL-4-, IL-17-, FoxP3- and IL-6 receptor (IL-6R)-expressing CD4(+) T cells in blood and/or pleural effusion samples of healthy donors, subjects with latent TB infection, and patients with active TB were analyzed by flow cytometry. Cytokines, transforming growth factor-beta and IL-6, in plasma and pleural fluid samples were determined by ELISA.


RESULTS
The frequency of Th17 cells in patients with active TB is significantly lower than those in healthy donors and individuals with latent TB infection. Correlation analysis showed that reduced Th17 responses observed in patients with active TB was significantly correlated with the decreased expression of IL-6R on CD4(+) T cells, but did not correlate with the concentrations of the cytokines, transforming growth factor-beta and IL-6. Consistently; in vitro study showed that M. tuberculosis products inhibit the expression of IL-6R on CD4(+) T cells.


CONCLUSIONS
Our results demonstrate that reduced Th17 responses were associated with the clinical outcome of M. tuberculosis infection. Suppression of Th17 response through down-regulation of IL-6R expression may be an important mechanism in the development of active TB.
Chen
Xinchun
X
Shenzhen-Hong Kong Institute of Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
Zhang
Mingxia
M
Liao
Mingfeng
M
Graner
Michael W
MW
Wu
Changyou
C
Yang
Qianting
Q
Liu
Haiying
H
Zhou
Boping
B
D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control
D001500:BCG Vaccine; D015415:Biomarkers; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D016212:Transforming Growth Factor beta