Immunological markers of lung disease due to non-tuberculous mycobacteria.

Lung disease due to non-tuberculous mycobacteria (NTM) is a poorly understood condition that is difficult to treat. Treatment remains problematic as few tools are available to help clinicians monitor disease progression or predict treatment outcome. In this study, plasma levels of several inflammatory molecules and the frequency of circulating T cell subsets were measured in patients with NTM lung disease and known treatment status, and compared with their adult offspring and with unrelated healthy controls. Plasma levels of the chemokine CXCL10 and IL-18 were assessed for associations with treatment efficacy. CXCL10 was higher in patients than adult offspring (p< 0.001) and unrelated controls (p< 0.001). Plasma CXCL10 was also lower in patients who responded well to therapy or who controlled their infection without requiring therapy, when compared to patients who did not respond to therapy (p=0.03). Frequencies of activated (HLA-DR(+)) CD4(+) T cells were higher in patients than adult offspring (p<0.001) and unrelated controls (p<0.05), with the highest frequencies in individuals who had completed at least 6 months of treatment. Frequencies of activated (CD38(+)) CD8(+) T cells in most treatment responders were similar to unrelated controls. Low plasma levels of CXCL10 may reflect successful control of NTM lung disease with or without therapy. Compared with responders, patients who responded poorly to treatment generally had higher plasma levels of CXCL10 and IL-18, and higher frequencies of activated CD8(+) T cells.

Susceptibility to pulmonary disease due to Mycobacterium avium-intracellulare complex may reflect low IL-17 and high IL-10 responses rather than Th1 deficiency.

It remains unclear why some individuals and not others are susceptible to non-tuberculous mycobacterial lung disease (NTMLD). To determine whether NTMLD is associated with defects or biases in Th1/Th2/Th17 immunity, blood leukocytes from NTM patients with nodular bronchiectasis, their adult offspring, and healthy population controls were stimulated with staphylococcal enterotoxin B (SEB), tuberculin and sensitin to measure cytokine production. In response to SEB, NTM patients exhibited higher frequencies of IFNγ-producing CD4(+) T cells than population controls (P<0.001). In supernatant, levels of IL-17 were lower in patients than adult offspring. Sensitin elicited higher IFNγ responses from patients than controls (P<0.05). Patients also produced more IL-10 in supernatant than controls after culture with tuberculin (P<0.01) or sensitin (P<0.05), but IL-10-producing CD4(+) T cells were undetectable. NTMLD is not associated with deficient IFNγ production, but may be associated with reduced Th17 immunity and/or a predisposition towards IL-10 production from non-CD4(+) T cells.