Differences in T-cell responses between Mycobacterium tuberculosis and Mycobacterium africanum-infected patients.
In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf- and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with TB-specific antigens. Before treatment, percentages of early secreted antigenic target-6(ESAT-6)/culture filtrate protein-10(CFP-10) and purified protein derivative-specific single-TNF-α-producing CD4(+) and CD8(+) T cells were significantly higher while single-IL-2-producing T cells were significantly lower in Maf- compared with Mtb-infected patients. Purified protein derivative-specific polyfunctional CD4(+) T cells frequencies were significantly higher before than after treatment, but there was no difference between the groups at both time points. Furthermore, the proportion of CD3(+) CD11b(+) T cells was similar in both groups pretreatment, but was significantly lower with higher TNF-α, IL-2, and IFN-γ production in Mtb- compared with that of Maf-infected patients posttreatment. Our data provide evidence of differences in T-cell responses to two mycobacterial strains with differing virulence, providing some insight into TB pathogenesis with different Mtb strains that could be prospectively explored as biomarkers for TB protection or susceptibility.
Vaccinology Theme, Medical Research Council Unit, The Gambia; Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Leopold D
LD
Tientcheu
Jayne S
JS
Sutherland
Bouke C
BC
de Jong
Beate
B
Kampmann
James
J
Jafali
Ifedayo M
IM
Adetifa
Martin
M
Antonio
Hazel M
HM
Dockrell
Martin O
MO
Ota
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D013045:Species Specificity; D014376:Tuberculosis / Q000097:blood / Q000276:immunology* / Q000473:pathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis
Cytokines; Mycobacterium africanum; Mycobacterium tuberculosis; T cells; Tuberculosis