Abstract
Granule-associated killing molecules released from cytotoxic T lymphocytes participate as a crucial step in immunity against tuberculosis (TB), but the role of coordinated production remains controversial. Coordinated release of effector molecules in vitro after stimulating peripheral blood mononuclear cells (PBMCs) of active TB or HIV/TB coinfection patients with PPD, purified protein derivative of tuberculin and avirulent Mtb, H37Ra, an attenuated strain were investigated in association with clinical outcomes. Perforin, granzyme-B, granulysin and IFN-γ were measured using ELISA. Before anti-TB treatment, PBMCs of TB stimulated with PPD or H37Ra released higher perforin, granzyme-B, and granulysin levels than in HIV/TB and released significantly higher IFN-γ (p = 0.045, p = 0.022). Granulysin positively correlated with perforin in TB (p = 0.042, r = 0.385), HIV/TB coinfection (p = 0.003, r = 0.941) after PPD stimulation, and after H37Ra stimulation in TB (p = 0.005, r = 0.549), but negatively correlated with granzyme B in TB (p = 0.042, r = −0.386), HIV/TB coinfection (p = 0.042, r = 0.754) were noted. After anti-TB treatment, increased levels of perforin, granulysin and IFN-γ in TB or HIV/TB upon PPD or H37Ra stimulation, and decreased granzyme-B levels after PPD (p = 0.003) or H37Ra (p = 0.028) stimulation in TB were observed. These results suggest that granulysin may act synergistic with perforin and IFN-γ in TB, indicating its crucial function in host immunity to tuberculosis. Future studies with larger numbers of patients ought to be conducted in the future.
Highlights
Tuberculosis (TB) in humans can progress to active disease with various clinical manifestations in about 5–10% of people infected with Mycobacterium tuberculosis (Mtb)
REVIEWthe in vitro levels of granulysin, perforin, granzyme-B and IFN-γ stain heat ative; 7 H37Ra = avirulent released from peripheral blood mononuclear cells (PBMCs) of active TB or HIV/TB coinfection patients after purified protein derivative (PPD) and H37Ra stimulation
T cells which participate as a crucial step in protective immunity against tuberculosis are needed to tailor control measures
Summary
Tuberculosis (TB) in humans can progress to active disease with various clinical manifestations in about 5–10% of people infected with Mycobacterium tuberculosis (Mtb). It is estimated that there were 10.4 million new TB cases and 480,000 new cases of multidrug-resistant TB (MDR-TB). Causing 1.4 million deaths in 2015 [1]. Directing to the activation of the innate immune defense mechanism, alveolar macrophages and dendritic cells recognize and phagocytose. In persistent TB, the innate immune responses by macrophages and neutrophils are of critical importance [3]. Even though macrophages are armed with a wide battery of antimicrobial mechanisms, the control of bacterial proliferation and TB clinical progression is mainly depending on the activation signals delivered from CD4+ T cells [4] and CD8+ T cells [5]
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