Immune Responses to Mycobacterium Tuberculosis (Mtb) in People With Latent Tuberculosis Infection With or Without Concomitant Helminth Infection

Mycobacterium tuberculosis (Mtb) infection remains an important cause of morbidity and mortality worldwide. A problem for eradication efforts is the large reservoir of \~2 billion people with latent tuberculosis (TB) infection (LTBI) and poor understanding of factors leading to active disease progression. Helminth infections geographically overlap with Mtb and induce significant immune-mediated modulation. Although CD4+T cells producing IFN-gamma and TNF-alpha have been implicated in protective immunity to TB, a detailed description of the evolution of protective and immunomodulatory responses in LTBI is lacking. Additionally, there is incomplete understanding of how the immunomodulation caused by helminth co-infection affects such responses. This protocol will attempt to fill this knowledge gap through comprehensive longitudinal immunological analyses of two populations of subjects with LTBI, with or without concurrent helminth infection (HEL+ and HEL- respectively). In both groups, venipuncture and possibly apheresis will be performed to understand protective and modulatory T cell and monocyte/macrophage responses. Subjects will receive treatment for helminth infection and treatment for LTBI will be offered according to current standard of care guidelines. Two groups of subjects within the LTBI group will be offered bronchoscopy and lavage --- (a) those with structural lung damage from prior treated/healed tuberculosis and (b) those with recent prolonged exposure (greater than or equal to 3 months) to a household contact with active TB. The primary objective is to evaluate CD4+ T cell responses and regulatory T cell responses in HEL+ and HEL- subjects with LTBI at the time of diagnosis (baseline). HEL+ subjects will then receive treatment for parasitic infection and both groups (HEL+ and HEL-) will be offered LTBI treatment. Evolution of the baseline TB-specific immune responses on and after LTBI treatment will then be studied. Additionally, baseline immune responses to mycobacteria will be contrasted in the HEL+ group with all time points post treatment for helminth infection. A secondary objective is to evaluate the immune phenotype and functionality of tissue resident immune cells obtained by bronchoalveolar lavage in subjects with LTBI and structural lung damage from prior treated/healed pulmonary tuberculosis as well as subjects with recent prolonged TB exposure from an active TB case irrespective of helminth infection status. An exploratory objective is to evaluate if there are subsets of subjects within the LTBI group (irrespective of helminth infection status) who have stable pool of long lasting antigen-specific IL-2 only producing CD4+ central memory T cells and changes to this pool after receiving LTBI treatment.