Promotion of a down-modulated lung immune state may be a strategy by M. tuberculosis to foster active disease and persistence.
One-third of humans carry Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) where microbe/host immune response interactions result in persistence or active TB. However, immune mediators associated with human TB remain poorly defined. Through a series of comparative studies of lung immune response of TB cases at the time of diagnosis and patients with other infectious lung diseases and volunteers, we found that TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity critical for containment of M. tuberculosis. Despite the concomitant heightened levels of Th1-type mediators, they are likely rendered ineffectual by high levels of intracellular (e.g., SOCS) and extracellular (e.g., IL-10) immune suppressors. These modulators are a direct response to M. tuberculosis as many suppressive factors declined to the levels of controls by 30 days of anti-TB treatment while most Th1-type and innate immune mediators rose above the pre-treatment levels. Parallel laboratory studies and monitored lung alveolar macrophage effector, nitric oxide synthase-2 (being shown critical for killing M. tuberculosis), support that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type/innate immunity as an immunopathological strategy. Our studies highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response.
Ho
John L
JL
Hospitalist Service, Southern Maine Medical Center, One Medical Center Drive, Biddeford, Maine 04005, USA. millennium.john@gmail.com
Lapa e Silva
Jose Roberto
JR
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
D016207:Cytokines