In vitro infection with Mycobacterium tuberculosis induces a distinct immunological pattern in blood from healthy relatives of tuberculosis patients

Abstract

Part of the susceptibility to tuberculosis has a genetic basis, which is clear in primary immunodeficiencies, but is less evident in apparently immunocompetent subjects. Immune responses were analysed in blood samples from tuberculosis patients and their healthy first-degree relatives who were infected in vitro with mycobacteria (either Mycobacterium tuberculosis or M. bovis BCG). The antimicrobial activity against M. tuberculosis in blood from relatives was significantly lower than that observed in healthy controls. Tuberculosis patients exhibited a higher number of neutrophils, and monocyte phagocytosis was inhibited in both relatives and tuberculosis patients. A remarkable finding was that the production of reactive oxygen species by infected neutrophils was higher in relatives than in healthy controls. A higher production of TNFα in infected blood from relatives was also observed. These results may indicate that relatives display a stronger inflammatory response and that their immune response to M. tuberculosis is different from those of unrelated controls. First-degree relatives may represent a highly informative group for the analysis of tuberculosis susceptibility.

Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among Mycobacterium tuberculosis exposed persons living with HIV

“…The multi-protein NADPH oxidase complex consists of multiple subunits (including cytosolic p40-phox, p47phox and p67-phox, as well as the catalytic gp91-phox subunit) and other proteins (transmembrane p22-phox and nucleotide-binding Rac2) and is involved in the process to produce ROS [46]. ROS is mostly known to modulate a pro-inflammatory effect, with increased levels positively correlated to higher levels of TNF and a greater control of Mtb PLOS GENETICS infection [47]. High levels of ROS can be damaging, but at lower levels ROS can mediate an anti-inflammatory effect in mouse neutrophils by inhibiting p-AKT and NF-κβ and inducing apoptosis [48][49][50][51][52][53].…”

Altered neutrophil extracellular traps in response toMycobacterium tuberculosisin persons living with HIV with no previous TB and negative TST and IGRA

“…The multi-protein NADPH oxidase complex consists of multiple subunits (including cytosolic p40-phox, p47phox and p67-phox, as well as the catalytic gp91-phox subunit) and other proteins (transmembrane p22-phox and nucleotide-binding Rac2) and is involved in the process to produce ROS (46). ROS is mostly known to modulate a pro-inflammatory effect, with increased levels positively correlated to higher levels of TNF and a greater control of Mtb infection (47)…”