title: Infection with Helicobacter pylori is associated with protection against tuberculosis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, United States of America. shnperry@stanford.edu
authors.forename: Sharon
authors.initials: S
authors.lastname: Perry
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.forename: Jay V
authors.initials: JV
authors.lastname: Solnick
authors.forename: Maria
authors.initials: M
authors.lastname: de la Luz Sanchez
authors.forename: Shufang
authors.initials: S
authors.lastname: Yang
authors.forename: Philana Ling
authors.initials: PL
authors.lastname: Lin
authors.forename: Lori M
authors.initials: LM
authors.lastname: Hansen
authors.forename: Najeeha
authors.initials: N
authors.lastname: Talat
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: Rabia
authors.initials: R
authors.lastname: Hussain
authors.forename: Richard A
authors.initials: RA
authors.lastname: Adegbola
authors.forename: Joanne
authors.initials: J
authors.lastname: Flynn
authors.forename: Don
authors.initials: D
authors.lastname: Canfield
authors.forename: Julie
authors.initials: J
authors.lastname: Parsonnet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D014374:Tuberculin Test; D014376:Tuberculosis / Q000150:complications*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007371:Interferon-gamma