The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis.
The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193-0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15-2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis.
Caws
Maxine
M
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam. mcaws@hotmail.com
Thwaites
Guy
G
Dunstan
Sarah
S
Hawn
Thomas R
TR
Lan
Nguyen Thi Ngoc
NT
Thuong
Nguyen Thuy Thuong
NT
Stepniewska
Kasia
K
Huyen
Mai Nguyet Thu
MN
Bang
Nguyen Duc
ND
Loc
Tran Huu
TH
Gagneux
Sebastien
S
van Soolingen
Dick
D
Kremer
Kristin
K
van der Sande
Marianne
M
Small
Peter
P
Anh
Phan Thi Hoang
PT
Chinh
Nguyen Tran
NT
Quy
Hoang Thi
HT
Duyen
Nguyen Thi Hong
NT
Tho
Dau Quang
DQ
Hieu
Nguyen T
NT
Torok
Estee
E
Hien
Tran Tinh
TT
Dung
Nguyen Huy
NH
Nhu
Nguyen Thi Quynh
NT
Duy
Phan Minh
PM
van Vinh Chau
Nguyen
N
Farrar
Jeremy
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005798:Genes, Bacterial; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014390:Tuberculosis, Meningeal / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D014744:Vietnam
D051195:Toll-Like Receptor 2