Association of ESAT-6/CFP-10-induced IFN-γ, TNF-α and IL-10 with clinical tuberculosis: evidence from cohorts of pulmonary tuberculosis patients, household contacts and community controls in an endemic setting

Abstract

Summary Mycobacterium tuberculosis (Mtb) early secreted protein antigen 6 (ESAT‐6) and culture filtrate protein 10 (CFP‐10) are among candidate vaccines against tuberculosis (TB). Results of experimental animal models show that these antigens are associated with induction of strong T cell immunity [interferon (IFN)‐γ production], while others report that these proteins as virulent factors involved in pathogenicity of Mtb infection. However, the role of ESAT‐6/CFP‐10 during natural Mtb infections in humans has not been established. In this paper we present results of a longitudinal study from an Mtb‐infected human population from an endemic setting. Whole blood assay was used to determine levels of IFN‐γ, tumour necrosis factor (TNF)‐α and interleukin (IL)‐10 against rESAT‐6/CFP‐10 in TB patients, household contacts and community controls. The levels of IFN‐γ, TNF‐α and IL‐10 against rESAT‐6/CFP‐10 at baseline were significantly higher in patients and community controls than in household contacts. In patients, no significant difference was observed in the level of these cytokines before and after chemotherapy whereas, in contacts, the level of these cytokines increased significantly and progressively over time. The study shows that the levels of IFN‐γ, TNF‐α and IL‐10 against rESAT‐6/CFP‐10 are depressed during Mtb infection or exposure but are elevated during clinical TB. Our findings from a study of naturally infected human population suggest that IFN‐γ, TNF‐α and IL‐10 against rESAT‐6/CFP‐10 are markers for clinical TB but not for protective immunity.

Anemia and Hematologic Characteristics in Newly Diagnosed Pulmonary Tuberculosis Patients at Diagnosis in Kinshasa

“…Such observation is not a surprisingin TB patients given the anorexia, the TNF-α related cachexia and other factors. TNF-α is abundantly produced during the macrophage invasion of bacilli [29] [30]. In addition, the underprivileged live related to the SES can also be seen as potential contributor to the low BMI.…”

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

“…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 immune‐dominant Mtb antigens. For instance, the level of IFN‐γ against ESAT‐6/CFP‐10 was significantly higher in untreated patients than in HHCs and CCs , while CCs had significantly higher levels of IFN‐γ against LAM and Rv2031 than untreated PTB patients and HHCs . However, the level of IFN‐γ against HBHA was significantly higher in HHCs and CCs than untreated patients .…”

“…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.…”