Mycobacterium africanum elicits an attenuated T cell response to early secreted antigenic target, 6 kDa, in patients with tuberculosis and their household contacts

被引:69
作者
de Jong, BC
Hill, PC
Brookes, RH
Gagneux, S
Jeffries, DJ
Otu, JK
Donkor, SA
Fox, A
McAdam, KPWJ
Small, PM
Adegbola, RA
机构
[1] MRC Labs, Banjul, Gambia
[2] Stanford Univ, Div Infect Dis & Geog Med, Stanford, CA 94305 USA
[3] Inst Syst Biol, Seattle, WA USA
基金
英国医学研究理事会;
关键词
D O I
10.1086/502977
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Mycobacterium africanum, a member of the M. tuberculosis complex that is infrequently found outside of western Africa, is the cause of up to half of the tuberculosis cases there. Methods. We genotyped mycobacterial isolates obtained from a study of patients with tuberculosis and their household contacts and compared T cell responses and tuberculin skin test results by infecting genotype. Results. The T cell response to early secreted antigenic target, 6 kDa ( ESAT-6), was attenuated in patients with tuberculosis ( odds ratio [ OR], 0.41 [ 95% confidence interval {CI}, 0.19-0.89]; p = .024) and household contacts ( OR, 0.56 [ 95% CI, 0.38-0.83]; P = .004) infected with M. africanum, compared with the response in those infected with M. tuberculosis. In these same groups, responses to culture filtrate protein, 10 kDa ( CFP-10), were nonsignificantly attenuated (P = .22 and P = .16, respectively), as were tuberculin skin test results (p = .30 and P = .46, respectively). Sequencing of region of difference 1 of M. africanum revealed that Rv3879c is a pseudogene in M. africanum; however, this finding does not provide an obvious mechanism for the attenuated ESAT-6 response. Conclusions. This is the first evidence, to our knowledge, that strain differences affect interferon-gamma-based T cell responses. Our findings highlight the need to test new diagnostic candidates against different strains of mycobacteria. Integrating additional immunologic and genomic comparisons of M. tuberculosis and M. africanum into further studies may provide fundamental insights into the interactions between humans and mycobacteria.
引用
收藏
页码:1279 / 1286
页数:8
相关论文
共 27 条
[1]   ESAT-6 proteins: protective antigens and virulence factors? [J].
Brodin, P ;
Rosenkrands, I ;
Andersen, P ;
Cole, ST ;
Brosch, R .
TRENDS IN MICROBIOLOGY, 2004, 12 (11) :500-508
[2]  
CASTETS M, 1969, Bulletin de la Societe Medicale d'Afrique Noire de Langue Francaise, V14, P693
[3]  
Castets M, 1968, Rev Tuberc Pneumol (Paris), V32, P179
[4]   Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells [J].
Chapman, ALN ;
Munkanta, M ;
Wilkinson, KA ;
Pathan, AA ;
Ewer, K ;
Ayles, H ;
Reece, WH ;
Mwinga, A ;
Godfrey-Faussett, P ;
Lalvani, A .
AIDS, 2002, 16 (17) :2285-2293
[5]   Mycobacterium africanum:: a new opportunistic pathogen in HIV infection? [J].
de Jong, BC ;
Hill, PC ;
Brookes, RH ;
Otu, JK ;
Peterson, KL ;
Small, PM ;
Adegbola, RA .
AIDS, 2005, 19 (15) :1714-1715
[6]  
Desmond E, 2004, EMERG INFECT DIS, V10, P921
[7]   Evolution of epitope-specific memory CD4+ T cells after clearance of hepatitis C virus [J].
Godkin, AJ ;
Thomas, HC ;
Openshaw, PJ .
JOURNAL OF IMMUNOLOGY, 2002, 169 (04) :2210-2214
[8]   Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis [J].
Gutierrez, M. Cristina ;
Brisse, Sylvain ;
Brosch, Roland ;
Fabre, Michel ;
Omais, Bahia ;
Marmiesse, Magali ;
Supply, Philip ;
Vincent, Veronique .
PLOS PATHOGENS, 2005, 1 (01) :55-61
[9]   Quantitative T cell assay reflects infectious load of Mycobacterium tuberculosis in an endemic case contact model [J].
Hill, PC ;
Fox, A ;
Jeffries, DJ ;
Jackson-Sillah, D ;
Lugos, MD ;
Owiafe, PK ;
Donkor, SA ;
Hammond, AS ;
Corrah, T ;
Adegbola, RA ;
McAdam, KPWJ ;
Brookes, RH .
CLINICAL INFECTIOUS DISEASES, 2005, 40 (02) :273-278
[10]   Large-scale evaluation of enzyme-linked immunospot assay and skin test for diagnosis of Mycobacterium tuberculosis infection against a gradient of exposure in The Gambia [J].
Hill, PC ;
Brookes, RH ;
Fox, A ;
Fielding, K ;
Jeffries, DJ ;
Jackson-Sillah, D ;
Lugos, MD ;
Owiafe, PK ;
Donkor, SA ;
Hammond, AS ;
Otu, JK ;
Corrah, T ;
Adegbola, RA ;
McAdam, KPWJ .
CLINICAL INFECTIOUS DISEASES, 2004, 38 (07) :966-973