RATIONALE: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). OBJECTIVES: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. METHODS: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. CONCLUSIONS: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.
RATIONALE: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). OBJECTIVES: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. METHODS: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. CONCLUSIONS: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.
Authors: A van Rie; R Warren; M Richardson; T C Victor; R P Gie; D A Enarson; N Beyers; P D van Helden Journal: N Engl J Med Date: 1999-10-14 Impact factor: 91.245
Authors: Qian Gao; Katharine E Kripke; Alok J Saldanha; Weihong Yan; Susan Holmes; Peter M Small Journal: Microbiology (Reading) Date: 2005-01 Impact factor: 2.777
Authors: Iñaki Comas; Jaidip Chakravartti; Peter M Small; James Galagan; Stefan Niemann; Kristin Kremer; Joel D Ernst; Sebastien Gagneux Journal: Nat Genet Date: 2010-05-23 Impact factor: 38.330
Authors: Abebech Demissie; Eliane M S Leyten; Markos Abebe; Liya Wassie; Abraham Aseffa; Getahun Abate; Helen Fletcher; Patrick Owiafe; Philip C Hill; Roger Brookes; Graham Rook; Alimuddin Zumla; Sandra M Arend; Michel Klein; Tom H M Ottenhoff; Peter Andersen; T Mark Doherty Journal: Clin Vaccine Immunol Date: 2006-02
Authors: Robin Wood; Stephen D Lawn; Judy Caldwell; Richard Kaplan; Keren Middelkoop; Linda-Gail Bekker Journal: PLoS One Date: 2011-10-10 Impact factor: 3.240
Authors: Stephanus T Malherbe; Shubhada Shenai; Katharina Ronacher; Andre G Loxton; Gregory Dolganov; Magdalena Kriel; Tran Van; Ray Y Chen; James Warwick; Laura E Via; Taeksun Song; Myungsun Lee; Gary Schoolnik; Gerard Tromp; David Alland; Clifton E Barry; Jill Winter; Gerhard Walzl; Lance Lucas; Gian van der Spuy; Kim Stanley; Lani Thiart; Bronwyn Smith; Nelita Du Plessis; Caroline G G Beltran; Elizna Maasdorp; Annare Ellmann; Hongjo Choi; Joonsung Joh; Lori E Dodd; Brian Allwood; Coenie Koegelenberg; Morné Vorster; Stephanie Griffith-Richards Journal: Nat Med Date: 2016-09-05 Impact factor: 53.440
Authors: Sebastian Carrasco Pro; Cecilia S Lindestam Arlehamn; Sandeep K Dhanda; Chelsea Carpenter; Mikaela Lindvall; Ali A Faruqi; Clark A Santee; Harald Renz; John Sidney; Bjoern Peters; Alessandro Sette Journal: PLoS One Date: 2018-05-07 Impact factor: 3.240
Authors: Aparna Nathan; Jessica I Beynor; Yuriy Baglaenko; Sara Suliman; Kazuyoshi Ishigaki; Samira Asgari; Chuan-Chin Huang; Yang Luo; Zibiao Zhang; Kattya Lopez; Cecilia S Lindestam Arlehamn; Joel D Ernst; Judith Jimenez; Roger I Calderón; Leonid Lecca; Ildiko Van Rhijn; D Branch Moody; Megan B Murray; Soumya Raychaudhuri Journal: Nat Immunol Date: 2021-05-24 Impact factor: 25.606