Infection with Helicobacter pylori Is Associated with Protection against Tuberculosis

• Published in: PloS one Vol. 5; no. 1; p. e8804
• Main Authors: Perry, Sharon, de Jong, Bouke C., Solnick, Jay V., Sanchez, Maria de la Luz, Yang, Shufang, Lin, Philana Ling, Hansen, Lori M., Talat, Najeeha, Hill, Philip C., Hussain, Rabia, Adegbola, Richard A., Flynn, JoAnne, Canfield, Don, Parsonnet, Julie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.01.2010; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allergies; Analysis of Variance; Animals; Antibodies; Antibodies, Bacterial - biosynthesis; Antigens; Antiulcer agents; Asthma; Asymptomatic infection; Bacterial infections; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Councils; Cynomolgus; Departments; Development and progression; Disease control; Exposure; Female; Health aspects; Helicobacter infections; Helicobacter Infections - complications; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - isolation & purification; Humans; Hypotheses; Immune response; Immunity; Immunology; Immunology/Immunity to Infections; Infections; Infectious diseases; Infectious Diseases/Gastrointestinal Infections; Infectious Diseases/Respiratory Infections; Interferon; Interferon-gamma - biosynthesis; Laboratory animals; Leukocytes (mononuclear); Macaca; Macaca fascicularis; Male; Medical research; Medicine; Microorganisms; Middle Aged; Multivariate analysis; Mutualism; Mycobacterium tuberculosis; Pathogens; Peripheral blood mononuclear cells; Population; Primates; Principal components analysis; Public Health and Epidemiology/Infectious Diseases; Serology; Skin tests; Socioeconomic factors; Stomach; Studies; Trends; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis - complications; Vaccine development; Vaccines; Variance analysis; Young Adult; γ-Interferon; Pakistan; California; Pittsburgh Pennsylvania; United States > US; Karachi Pakistan; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008804

Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04). H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.