Resistance to Latent Mycobacterium tuberculosis Infection in Uganda: Immunologic Profiling

Despite significant exposure to Mycobacterium tuberculosis (Mtb), some humans remain uninfected, as defined by persistently negative immune sensitization tests (tuberculin skin test, TST; interferon gamma release assays, IGRA). To explore mechanisms of natural resistance to Mtb infection, we profiled tissues from highly-exposed Mtb contacts from Uganda. The cohort from this submission were household contacts of pulmonary tuberculosis cases who were followed longitudinally over 8 years and maintained negative TST and IGRA testing on serial evaluations. This cohort is well-described (Stein et al. 2019, PMID: 30165605).]]>
Inclusion and exclusion criteria of the parent Kawempe Community Health Study (Kampala, Uganda) are published (Stein et al., 2018, PMID: 29304247; Stein et al., 2019, PMID: 30165605). For each immune profiling assay, we defined Mtb ‘resister' (RSTR) cases as those that maintained negative TST and IGRA testing at all sampling times. Controls with latent Mtb infection (LTBI) were those with concordant, positive TST and IGRA testing at all sampling dates, who showed no clinical evidence of tuberculosis disease. Unless otherwise stated, HIV-positive cases and controls were excluded.]]>
Index cases with pulmonary TB and any household contacts were recruited in the Kawempe Community Health Study (Kampala, Uganda) from 2002-2012 (Stein et al., 2018, PMID 29304247) and serial TST testing was performed over 2 years. A subset was followed after 8+ years to repeat TST and obtain IGRA (Quantiferon Gold In-tube) x 3 (Stein et al., 2019, PMID: 30165605). The immunologic profiling study derived peripheral blood mononuclear cells and whole blood (Paxgene RNA) from these subjects for ex-vivo culture experiments or direct sequencing, respectively.]]>