Tobacco smoke exposure recruits inflammatory airspace monocytes that establish permissive lung niches for Mycobacterium tuberculosis.

Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive to Mycobacterium tuberculosis (Mtb) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current and never smokers by performing single-cell RNA sequencing (scRNA-seq), flow cytometry, and functional assays. We observed the enrichment of immature inflammatory monocytes in the lungs of smokers compared with nonsmokers. These monocytes exhibited phenotypes consistent with recent recruitment from blood, ongoing differentiation, increased activation, and states similar to those with chronic obstructive pulmonary disease. Using integrative scRNA-seq and flow cytometry, we identified CD93 as a marker for a subset of these newly recruited smoking-associated lung monocytes and further provided evidence that the recruitment of monocytes into the lung was mediated by CCR2-binding chemokines, including CCL11. We also show that these cells exhibit elevated inflammatory responses upon exposure to Mtb and accelerated intracellular growth of Mtb compared with mature macrophages. This elevated Mtb growth could be inhibited by anti-inflammatory small molecules, providing a connection between smoking-induced pro-inflammatory states and permissiveness to Mtb growth. Our findings suggest a model in which smoking leads to the recruitment of immature inflammatory monocytes from the periphery to the lung, which results in the accumulation of these Mtb-permissive cells in the airway. This work defines how smoking may lead to increased susceptibility to Mtb and identifies host-directed therapies to reduce the burden of TB among those who smoke.

Plasma-Treated Air and Water-Assessment of Synergistic Antimicrobial Effects for Sanitation of Food Processing Surfaces and Environment.

The synergistic antimicrobial effects of plasma-processed air (PPA) and plasma-treated water (PTW), which are indirectly generated by a microwave-induced non-atmospheric pressure plasma, were investigated with the aid of proliferation assays. For this purpose, microorganisms (Listeria monocytogenes, Escherichia coli, Pectobacterium carotovorum, sporulated Bacillus atrophaeus) were cultivated as monocultures on specimens with polymeric surface structures. Both the distinct and synergistic antimicrobial potential of PPA and PTW were governed by the plasma-on time (5⁻50 s) and the treatment time of the specimens with PPA/PTW (1⁻5 min). In single PTW treatment of the bacteria, an elevation of the reduction factor with increasing treatment time could be observed (e.g., reduction factor of 2.4 to 3.0 for P. carotovorum). In comparison, the combination of PTW and subsequent PPA treatment leads to synergistic effects that are clearly not induced by longer treatment times. These findings have been valid for all bacteria (L. monocytogenes > P. carotovorum = E. coli). Controversially, the effect is reversed for endospores of B. atrophaeus. With pure PPA treatment, a strong inactivation at 50 s plasma-on time is detectable, whereas single PTW treatment shows no effect even with increasing treatment parameters. The use of synergistic effects of PTW for cleaning and PPA for drying shows a clear alternative for currently used sanitation methods in production plants. Highlights: Non-thermal atmospheric pressure microwave plasma source used indirect in two different modes-gaseous and liquid; Measurement of short and long-living nitrite and nitrate in corrosive gas PPA (plasma-processed air) and complex liquid PTW (plasma-treated water); Application of PTW and PPA in single and combined use for biological decontamination of different microorganisms.