Mycobacterium tuberculosis Catalase Inhibits the Formation of Mast Cell Extracellular Traps

Abstract

Tuberculosis is one of the leading causes of human morbidity and mortality. Mycobacterium tuberculosis (Mtb) employs different strategies to evade and counterattack immune responses persisting for years. Mast cells are crucial during innate immune responses and help clear infections via inflammation or by direct antibacterial activity through extracellular traps (MCETs). Whether Mtb induce MCETs production is unknown. In this study, we report that viable Mtb did not induce DNA release by mast cells, but heat-killed Mtb (HK-Mtb) did. DNA released by mast cells after stimulation with HK-Mtb was complexed with histone and tryptase. MCETs induced with PMA and HK-Mtb were unable to kill live Mtb bacilli. Mast cells stimulated with HK-Mtb induced hydrogen peroxide production, whereas cells stimulated with viable Mtb did not. Moreover, MCETs induction by HK-Mtb was dependent of NADPH oxidase activity, because its blockade resulted in a diminished DNA release by mast cells. Interestingly, catalase-deficient Mtb induced a significant production of hydrogen peroxide and DNA release by mast cells, indicating that catalase produced by Mtb prevents MCETs release by degrading hydrogen peroxide. Our findings show a new strategy employed by Mtb to overcome the immune response through inhibiting MCETs formation, which could be relevant during early stages of infection.

Paired acute‐baseline serum tryptase levels in perioperative anaphylaxis: An observational study

“…Issues related to specificity likely include the small increases in sAT concentrations occurring with random variations or nonanaphylactic events, and mechanisms of anaphylaxis that do not involve MC degranulation . Indeed, MC activation has been reported in atherosclerosis‐related cardiovascular events, coagulation abnormalities, and response to infectious agents . In line with previous cohorts, our results confirm that the consensus algorithm sAT >([1.2 × sBT] + 2) μg/L is a good compromise between empirical thresholds such as >(1.35 × sBT), which privileged sensitivity as high as 0.91 in previous literature and 0.81 in our study, or (sBT + 3) μg/L, which resulted in sensitivity values as low as 0.63 in the literature and 0.72 in our hands.…”

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

“…Bone marrow‐derived mast cells (BMMC) are commonly obtained by culturing with combinations of IL‐3 and stem cell factor (SCF). However, as reports have shown that chronic exposure to SCF results in attenuated FcεRI signaling and degranulation of mast cells, here we have used cultures of bone marrow from 6 to 8‐week‐old C57BL/6 female mice in the presence of IL‐3 alone, as described 11,12 . Mast cell purity was ≥95% as determined by flow cytometry after staining of CD117 (clone: 2B8; BioLegend, San Diego, CA, USA) and FcεRI (clone: MAR‐1; BioLegend, San Diego, CA, USA) (Fig.…”

Human mast cells exhibit an individualized pattern of antimicrobial responses

“…This mechanism is novel in hMCs, which have so far been described to form extracellular traps (ETs) while undergoing NADPH-dependent cell death. [19][20][21] In neutrophils, the latter type of ET production is termed "suicidal NETosis" as it leads to cell death. 14 However, in response to S. aureus Pilsczek et al 18 described a second ROS independent mechanism in neutrophils called "vital NETosis" in which the release of DNA occurs by fusion of DNA-containing vesicles with the plasma membrane.…”

“…MC lines and rodent MCs have been shown to release DNA using microscopy techniques. [19][20][21]27 To investigate whether the release of extracellular DNA in hMCs was associated with the formation of extracellular traps, cells were incubated with L. monocytogenes for 16 hours and colocalization of extracellular DNA (DAPI staining) and MC granule content release (tryptase staining) was analyzed by confocal microscopy. As shown in Figure 5, L. monocytogenes-stimulated hMCs showed externalized DNA ( Figure 5A) that colocalized with tryptase compared with unstimulated controls ( Figure 5B).…”

“…For instance, DNA release is observed after L. monocytogenes or E. faecalis encounter, whereas release of DNA is inhibited after M. tuberculosis exposure. 19,21 We hypothesized that different microbes induce individual patterns of functional response by MCs, including degranulation, chemokine secretion, and DNA release in the presence or absence of ROS production. We, therefore, assessed human mast cell (hMC) responses after their encounter with bacteria typically localized at tissue interfaces: Escherichia coli (gut commensal), L. monocytogenes (foodborne intracellular pathogen), Staphylococcus aureus (skin commensal and opportunistic pathogen), and Streptococcus pneumoniae (upper respiratory tract commensal and lung pathogen).…”