Human Lung Immunity againstMycobacterium tuberculosis

Abstract

The study of human pulmonary immunity against Mycobacterium tuberculosis (M.tb) provides a unique window into the biological interactions between the human host and M.tb within the broncho-alveolar microenvironment, the site of natural infection. Studies of bronchoalveolar cells (BACs) and lung tissue evaluate innate, adaptive, and regulatory immune mechanisms that collectively contribute to immunological protection or its failure. In aerogenically M.tb-exposed healthy persons lung immune responses reflect early host pathogen interactions that may contribute to sterilization, the development of latent M.tb infection, or progression to active disease. Studies in these persons may allow the identification of biomarkers of protective immunity before the initiation of inflammatory and disease-associated immunopathological changes. In healthy close contacts of patients with tuberculosis (TB) and during active pulmonary TB, immune responses are compartmentalized to the lungs and characterized by an exuberant helper T-cell type 1 response, which as suggested by recent evidence is counteracted by local suppressive immune mechanisms. Here we discuss how exploring human lung immunity may provide insights into disease progression and mechanisms of failure of immunological protection at the site of the initial host-pathogen interaction. These findings may also aid in the identification of new biomarkers of protective immunity that are urgently needed for the development of new and the improvement of current TB vaccines, adjuvant immunotherapies, and diagnostic technologies. To facilitate further work in this area, methodological and procedural approaches for bronchoalveolar lavage studies and their limitations are also discussed.

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria

“…However, given the invasive nature and the associated risk of bronchoscopy, especially in HIV-infected persons, a longitudinal study was judged not to be justifiable. Furthermore, the alveolar lymphocyte counts from HIV-uninfected individuals were higher than has been reported previously (4,5,40). Household indoor air pollution is highly prevalent in Malawi (41) and it is possible that this group of individuals had ongoing alveolar inflammation.…”

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

“…TB is primarily a disease of the lung (9,10). In advanced HIV infection, with severely reduced CD4 cell counts, TB infection is common, but there is reduced tissue destruction and cavitation rarely occurs (11).…”

Increased frequencies of pulmonary regulatory T-cells in latentMycobacterium tuberculosisinfection

“…Their findings, however, underline that in patients without active TB, the correlation between systemic and local immune response to M. tuberculosis varies. Since BAL cells are strikingly different from PBMCs cells in terms of functional capabilities and phenotype, one potential reason includes the discordant recognition of antigens [44]. Mycobacterial uptake, accessory function and infectability of alveolar macrophages are greater than that of PBMCs, with potential implications for antigen presentation [44].…”