Lipoarabinomannan‐specific TNF‐α and IFN‐γ as markers of protective immunity against tuberculosis: a cohort study in an endemic setting

Abstract

Lipoarabinomannan (LAM) is a virulent factor used for entry and survival of Mycobacterium tuberculosis (Mtb) in macrophages. Although the role of LAM for the diagnosis of tuberculosis (TB) has been extensively investigated, its cytokine response during natural Mtb infection in humans is largely unknown. In this study, LAM-specific IFN-γ, TNF-α, and IL-10 levels following whole blood assay were measured in untreated pulmonary TB patients, their contacts and community controls at baseline. In treated patients and contacts, cytokines were also measured at 6 and 12 months. At entry, 52.8% and 74.8% of controls and contacts were QFT-GIT positive, respectively. At baseline, untreated TB patients and contacts had significantly lower IFN-γ and TNF-α response compared to community controls (p < 0.0001). Besides, untreated patients had significantly higher TNF-α and IL-10 response compared to their contacts (p < 0.0001). At 6 months, contacts and treated TB patients had significantly increased INF-γ and TNF-α response (p < 0.0001). In TB patients, IFN-γ increased 10-fold following chemotherapy suggesting its potential role for treatment monitoring. The data suggests that LAM might have an anti-inflammatory effect during clinical TB and early Mtb infection. The data also suggests that LAM-induced IFN-γ and TNF-α could be used as biomarkers of protective immunity.

IFN‐γ against the 38‐kDa antigen of Mycobacterium tuberculosis discriminates pulmonary tuberculosis from infection and infection from exposure: evidence from a study of human population in a high endemic setting

“…In agreement with our observation, a study in Brazil has reported that IFN-c response to the 38 KDa/CFP-10 showed an increasing tendency in treated TB patients (12). Although we have reported a similar observations in the levels of IFN-c against recombinant HBHA (20), Rv2031 (21), and LAM (23), this is the first report from cohort study to show that Mtb suppresses the production of IFN-c against the 38 kDa during Mtb infection or clinical TB. Earlier studies in the murine model (11,29,30) have shown that the 38-kDa antigen is a potent inducer of T-cell immunity.…”

“…However, the level of IFN‐γ against HBHA was significantly higher in HHCs and CCs than untreated patients . Similarly, the level of IL‐10 against ESAT‐6/CFP‐10 , HBHA , and LAM was significantly higher in untreated PTB patients than in CCs, while IL‐10 against Rv2031 was the highest in CCs compared with untreated patients and HHCs.…”

“…The results show that there is a significant variation in cytokine responses against these immunedominant Mtb antigens. For instance, the level of IFN-c against ESAT-6/CFP-10 was significantly higher in untreated patients than in HHCs and CCs (22), while CCs had significantly higher levels of IFN-c against LAM and Rv2031 than untreated PTB patients and HHCs (21,23). However, the level of IFN-c against HBHA was significantly higher in HHCs and CCs than untreated patients (20).…”

“…In addition to the present study, we have earlier analyzed IFN‐γ, TNF‐α, and IL‐10 responses against ESAT‐6/CFP‐10 , HBHA , Rv2031 , and LAM in the same study population. The results show that there is a significant variation in cytokine responses against these immune‐dominant Mtb antigens.…”

“…Detailed description of the study area and the population has been given elsewhere . Earlier, we have published cytokine responses to immune‐dominant Mtb antigens such as HBHA , Rv2031 , ESAT‐6/CFP‐10 , and lipoarabinomannan from the same study population.…”