TABLE 2.

Comparison of combined CS exposure and M. tuberculosis infection experiments in vivo

CS exposure	TB infection	Key findings	Reference
Female C57BL/6 Whole body exposure Teague Enterprises, Davis, CA, USA 1× 1R4F cigarette 2 h exposure twice per day 5 days per week for 6 weeks	10–25 CFU Mtb Erdman via aerosol No CS exposure post-infection Harvest 28 days post-infection	CS exposure results in: ↓ frequency of IFN-γ+ T-cells in lungs and spleens ↓ c-Jun, ATF2 and CREB expression in lungs ↑ Mtb burden in lungs ↓ Mtb antigen-specific T-cell responses post-vaccination	[139]
Female C57BL/6 mice Whole body exposure Teague Enterprises, Davis, CA, USA 170–180× 3R4F cigarettes 5 h exposure twice per day 5 days per week for 14 weeks	10–25 CFU Mtb Erdman via aerosol No CS exposure post-infection Harvest 1, 7, 14 and 30 days post-infection	CS exposure results in: ↓ number of lung macrophages and DCs producing TNF and IL-12 ↑ number of lung macrophages and DCs producing IL-10 ↓ number of CD4+ T-cells producing IFN-γ and TNF in lungs and spleens ↑ Mtb burden in lungs and spleen from day 14 post-infection ↑ Mtb lung lesion area in lungs	[118]
Female C57BL/6 mice Whole body exposure SIU-48, Promech Lab AB, Vintrie, Sweden 12× 2R4F cigarettes 50 min exposure twice per day 5 days per week for 6 weeks	104 CFU Mtb H37Rv intranasally No CS exposure post-infection Harvest 28 and 42 days post-infection OR 0.5×106 CFU BCG intratracheally CS exposure post-infection Harvest 28 days post-infection	CS exposure results in: ↓ number of CD4+IFN-γ+ T-cells in lungs ↑ frequency of CD4+IL-4+ T-cells in lungs ↓ RANTES concentration in BALF ↓ TNF, IL-12, IFN-γ and NO production by lung mononuclear cells ↑ Mtb burden in lungs and spleens ↓ Mtb granuloma size, number and cellular infiltration	[149]

CS: cigarette smoke; TB: tuberculosis; CFU: colony-forming units; IFN: interferon; ATF2: activating transcription factor 2; CREB: cAMP response element-binding protein; Mtb: Mycobacterium tuberculosis; DC: dendritic cells; TNF: tumour necrosis factor; IL interleukin; CD: cluster of differentiation; BCG: bacille Calmette–Guérin; BALF: bronchoalveolar lavage fluid; NO: nitric oxide.