To Compare the Difference of Inflammasome Response of Inflammatory Macrophage Clinical Trial
Official title:
The Role of Inflammasome in Inflammatory Macrophage in Mycobacterium Avium Complex-lung Disease and Mycobacterium Abscessus-lung Disease
1. To investigate the inflammasome response of inflammatory and resting macrophage derived
from healthy human participants by stimulation using MAC or MAB bacilli.
2. To compare the difference of inflammasome response of inflammatory macrophage by
MAC/MAB bacilli stimulation between MAC/MAB-LD patients and the colonizers.
3. To study the diagnostic aid from immunological markers in inflammasome response in
inflammatory macrophage stimulated by MAC/MAB.
Lung disease (LD) due to nontuberculous mycobacteria (NTM) becomes an important clinical
concern, because the incidence and prevalence of NTM-LD have increased over the last decade.
Among the NTM-LD in Taiwan, Mycobacterium avium complex (MAC) and M. abscessus (MAB) are the
most frequent pathogenic species. Because MAC and MAB exist in the environment ubiquitously,
clinical relevance of MAC isolated in sputum is only around 35~42%, and that of MAB is
around 33%. According to the guideline of the American Thoracic Society, the diagnosis of
MAC-LD and MAB-LD is based on clinical, radiographic, and mycobacteriologic criteria. For
microbiology criteria, two or more sets of positive sputum mycobacterial culture for the
same NTM species within one year is required. Actually, mycobacteria culture is neither
timely nor efficient, which needs weeks to wait the results, especially for the slowly
growing NTM. Moreover, the nucleic acid amplification method cannot discriminate true NTM
infection and solely colonization because airway NTM colonization is not uncommon.
Therefore, diagnosis of true NTM-LD is a big challenge in clinical practice. However, to
early diagnose and then start treatment of NTM-LD is important because NTM-LD may be rapid
lethal in critical status or in patients without early proper treatment. Hence, more rapid
and accurate diagnostic test should be developed.
The body inflammatory markers are probably indicators for differentiating true NTM-LD from
pulmonary colonization and interferon-gamma (IFN-g) play a critical role in protective
immunity to mycobacterial infections. However, serum IFN-g poorly correlated with diagnosis
of NTM-LD and possibly due to the hosts with attenuated cellular immunity and the presence
of IFN-gamma inhibitor. By contrast, macrophages are the first-line defense while
mycobacterial bacilli enter through airway and may play an important role while MAC/MAB
infection. Macrophages can be polarized to inflammatory type and promotes type 1 immunity.
In addition, inflammatory macrophages can react through inflammasome to defense
intracellular mycobacteria. However, the inflammasome responses in inflammatory macrophages
are rarely investigated in MAC-LD and MAB-LD, either for the defense mechanism or its
diagnostic aid for disease form colonization. The investigators therefore conduct an
in-vitro inflammatory macrophage stimulation using MAC or MAB bacilli to observe the
difference of inflammasome response between MAC/MAB patients, colonizers, and controls.
;
Observational Model: Cohort, Time Perspective: Prospective