A Study of the Natural Immune Reaction to Mycobacterial Isolates of Human | Original Article

ABSTRACT:

Mycobacterium tuberculosis (M. tb) causes TB and kills millions worldwide. Immune-dependent tissue-damaging inflammation promotes aerosol transmission, making this disease ubiquitous. Since Type I IFNs play a debatable role in TB and their induction precedes clinical tuberculosis in patients, this study sought to identify a pattern (absolute levels and relative ratios) in interferon and regulatory molecule expression levels that correspond with TB patients and pulmonary versus extra pulmonary TB. Using an in vitro M. tb THP-1 infection model and antibody-based neutralization of specific interferons, we found that modulating interferon production promotes intracellular bacterial burden or clearance. Real-time PCR was performed to compare IFN alpha, beta, and gamma fold mRNA expression in 123 untreated TB patients (PTB - 56 EPTB - 67) and 86 healthy family contacts clinically clear of TB. EPTB and PTB patients' three IFN expression levels were compared. ELISA for Interleukin-1β, -1α, and Prostaglandin E2 was done on sera from 62 TB patients and 18 healthy contacts from the same residence. TB patients expressed more IFN-α than counterparts. IFN-α had the highest median fold mRNA expression (0.80) in untreated TB patients. PTB patients had a median fold mRNA expression level of IFN- (0.87) that was higher than EPTB patients'. EPTB patients expressed 0.81 times more IFN-α than PTB patients. The three IFNs were measured in matched samples from each patient at enrolment and after treatment. IFN-β and IFN- reduced considerably after therapy. IFN-α high or IFN-β low patients and contacts were then identified. All samples tested by ELISA had IFN- levels below detection. Every sample has PGE2. IL-1 detection vary. PGE2 and IFN- levels were found inversely correlated. These data suggest measuring type I IFNs may help monitor therapy response. The pattern of IFNs in patients (host factors) and the identification of acid-fast bacilli (AFB) by conventional smear microscopy (mycobacterial factors) are expected to occur earlier and precede mycobacterial load reduction.