Influenza Virus-Induced Lung Inflammation Was Modulated by Cigarette Smoke Exposure in Mice

Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1) or avian H9N2 (H9N2/G1) virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4⁺ and CD8⁺ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed mice, which might partially be attributed to the immunosuppressive effect of nicotine.     

Effects of curcumin on the activities of the enzymes that hydrolyse adenine nucleotides in platelets from cigarette smoke-exposed rats

The aim of the present study was to investigate the effect of curcumin (Cur) on the activity of ectonucleoside triphosphate diphosphohydrolase (CD39), 5'‐nucleotidase (CD73) and adenosine deaminase in platelets of cigarette smoke‐exposed rats. For that purpose, we subjected male Wistar rats to a treatment with Cur and cigarette smoke, once a day, 5 days each week, for 30 days. The rats were treated by gavage with Cur or corn oil and then exposed to cigarette smoke. The experimental procedures were divided into two sets of experiments. In the first, the animals were divided into four groups: vehicle (corn oil) or Cur 12·5, 25 or 50 mg·kg^‐1. In the second, the animals were divided into five groups: vehicle (corn oil), smoke, or smoke and Cur 12·5, 25 or 50 mg·kg^‐1. The results showed that treatment with Cur significantly prevented the increased adenosine triphosphate (ATP) (121%) and adenosine monophosphate (AMP) (159%) and the decreased adenosine diphosphate (ADP) (51%) hydrolysis observed in the cigarette smoke‐exposed rats Our results suggest that those purinergic enzyme alterations observed in the cigarette smoke‐exposed rats could be related to an excessive platelet aggregation and point toward the potential of Cur to modulate purinergic signalling and, consequently, regulate the thrombus formation. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparisons of Acids in Smoke of Lamina and Midrib of Flue-cured Tobacco Leaves

Acids of lamina and midrib cigarette smoke were converted into trimethylsilyl derivatives and they were analyzed with glass capillary column gas chromatography. Then compositional differences of acids between lamina and midrib cigarette smoke were discussed. The concentrations of organic acids were higher for lamina cigarette smoke than for midrib cigarette smoke. Large concentration difference were found in formic, acetic, propionic, lactic, glycolic, furoic, benzoic, phenylacetic, fumalic and m-hydroxybenzoic acid. Succinic and methylsuccinic acid were similar in lamina smoke and in midrib smoke.

A large amount of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one(amino-carbonyl reaction product) was identified for the first time in lamina smoke.     

Deadly triplex: Smoke,autophagy and apoptosis

Autophagy, a cellular program for organelle and protein turnover, represents primarily a cell survival mechanism. However, the role of autophagy in the regulation of apoptosis remains unclear. We have observed increases in morphological and biochemical indicators of autophagy in human lung from patients with chronic obstructive pulmonary disease (COPD). Furthermore, we observed induction of autophagic markers in mouse lung subjected to chronic cigarette smoke exposure. Recently, we investigated the role of the autophagic protein microtubule-associated protein 1 light chain 3B (LC3B) as a regulator of lung cell death. We found that LC3B knockout (LC3B^-/-) mice subjected to chronic cigarette smoke exposure have reduced lung apoptosis, and resist airspace enlargement, relative to wild-type mice. We therefore examined the mechanisms by which LC3B can regulate apoptosis in epithelial cells. We found that LC3B forms a complex with the death receptor Fas in lipid rafts of epithelial cells, which requires the caveolae-resident protein caveolin-1. Genetic interference of caveolin-1 in epithelial cells augments cigarette smoke-induced apoptosis. Caveolin-1 knockout mice exhibit increased autophagic markers, apoptosis, and airspace enlargement in the lung in response to chronic cigarette smoke. These studies demonstrate that LC3B can promote tissue injury during chronic cigarette smoke exposure, and suggest a mechanism by which LC3B, through interactions with caveolin-1 and Fas, can regulate apoptosis. Targeting the autophagic pathway may represent an experimental therapeutic strategy when designing new approaches to COPD treatment.     

Aging does not Enhance Experimental Cigarette Smoke-Induced COPD in the Mouse

It has been proposed that the development of COPD is driven by premature aging/premature senescence of lung parenchyma cells. There are data suggesting that old mice develop a greater inflammatory and lower anti-oxidant response after cigarette smoke compared to young mice, but whether these differences actually translate into greater levels of disease is unknown. We exposed C57Bl/6 female mice to daily cigarette smoke for 6 months starting at age 3 months (Ayoung@) or age 12 months (Aold@), with air-exposed controls. There were no differences in measures of airspace size between the two control groups and cigarette smoke induced exactly the same amount of emphysema in young and old. The severity of smoke-induced small airway remodeling using various measures was identical in both groups. Smoke increased numbers of tissue macrophages and neutrophils and levels of 8-hydroxyguanosine, a marker of oxidant damage, but there were no differences between young and old. Gene expression studies using laser capture microdissected airways and parenchyma overall showed a trend to lower levels in older animals and a somewhat lesser response to cigarette smoke in both airways and parenchyma but the differences were usually not marked. Telomere length was greatest in young control mice and was decreased by both smoking and age. The senescence marker p21^Waf1 was equally upregulated by smoke in young and old, but p16^INK4a, another senescence marker, was not upregulated at all. We conclude, in this model, animal age does not affect the development of emphysema and small airway remodeling.     

The effect of cigarette smoke on the metabolism of arachidonic acid in isolated hamster lungs

The effects of cigarette smoke on the metabolism of exogenous arachidonic acid (AA) were investigated in isolated hamster lungs. Arachidonate was injected into the pulmonary circulation and the metabolites were analysed from the nonrecirculating perfusion effluent by thin layer chromatography. After the pulmonary injection of 66 nmol of ¹⁴C-AA about 20 % of the injected radioactivity appreated in the perfusion effluent mostly as metabolites in six minutes. When isolated lungs were ventilated with cigarette smoke during the perfusion, the amounts of PGF_2α, PGE₂ and two unidentified metabolite groups increased in the lung effluent. In two other experimental series hamsters were exposed to cigarette smoke before the lung perfusion either once for 30 min or during one hour daily for ten consecutive days. Neither pre-exposures caused any changes in the amounts of arachidonate metabolites in the lung effluent.     

Cardiac-Specific Overexpression of Metallothionein Rescues against Cigarette Smoking Exposure-Induced Myocardial Contractile and Mitochondrial Damage

Objectives

Second hand cigarette smoke is an independent risk factor for cardiovascular disease. Although a tie between smoking and cardiovascular disease is well established, the underlying mechanisms still remains elusive due to the lack of adequate animal models. This study was designed to use a mouse model of exposure to cigarette smoke, a surrogate of environmental tobacco smoke, to evaluate the impact of cardiac overexpression of heavy metal scavenger metallothionein on myocardial geometry, contractile and intracellular Ca²⁺ properties and apoptosis following side-stream smoke exposure.

Methods

Adult male wild-type FVB and metallothionein transgenic mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte contractile and intracellular Ca²⁺ properties, fibrosis, apoptosis and mitochondrial damage were examined.

Results

Our data revealed that smoke exposure enlarged ventricular end systolic and diastolic diameters, reduced myocardial and cardiomyocyte contractile function, disrupted intracellular Ca²⁺ homeostasis, facilitated fibrosis, apoptosis and mitochondrial damage (cytochrome C release and aconitase activity), the effects of which were attenuated or mitigated by metallothionein. In addition, side-stream smoke expose enhanced phosphorylation of Akt and GSK3β without affecting pan protein expression in the heart, the effect of which was abolished or ameliorated by metallothionein. Cigarette smoke extract interrupted cardiomyocyte contractile function and intracellular Ca²⁺ properties, the effect of which was mitigated by wortmannin and NAC.

Conclusions

These data suggest that side-stream smoke exposure led to myocardial dysfunction, intracellular Ca²⁺ mishandling, apoptosis, fibrosis and mitochondrial damage, indicating the therapeutic potential of antioxidant against in second smoking-induced cardiac defects possibly via mitochondrial damage and apoptosis.     

Scavenging of free radicals in gas-phase mainstream cigarette smoke by immobilized catalase at filter level

Catalase is well known as capable of inducing the decomposition of H₂O₂. In this study, a kind of immobilized catalase (entrapped in cross-linked chitosan beads) was dispersed in conventional acetate filter as an antioxidant additive. Quantitative estimation of the free radicals in mainstream cigarette smoke (MCS) was performed to address the effect of this modified filter. It was found that the levels of PBN adduct and NO^?/NO₂^? associated with the gas-phase mainstream cigarette smoke (GPCS) were efficiently decreased by ～40% through catalase filtering. Besides, the modified filter was found to lower the MCS-induced adverse biological effects including lipid peroxidation and mutagenicity. This was proved to be substantially attributed to the catalase-dependent breakdown of NO^?, which was stimulated by some of peroxides (most probably being H₂O₂), the dismutation products of tar particulate matters (TPM). These results highlighted a promising approach to reduce the smoking-associated health risks to passive smokers. Moreover, the mechanisms of catalase filtering may be helpful for the development of appropriate immobilized enzyme systems to be applied for reducing health risks associated with gaseous pollutants.     

Biochemical Effects of Gamma Radiation on Potato and Sweet Potato Tissues

Relationship between the chemical constituents of tobacco leaves and the gaseous constituents of cigarette smoke from which K value¹⁾ was computed was discussed and the following presuppositions were demonstrated to be correct.

1. Fibrous substances in tobacco leaves are the main precursors of acetaldehyde, propionaldehyde, acrolein, acetone, methylethylketone, diacetyl, methanol, furan, an unknown compound, No. 6 and an unknown compound, No. 16 in cigarette smoke.

2. Sugars in tobacco leaves are the main precursors of 2-methylfuran and 2,5-dimethyl- furan in cigarette smoke.

3. Resinous substances in tobacco leaves are the main precursors of isoprene and an unknown compound, No. 2 in cigarette smoke.

     

Irreversible inhibition of monoamine oxidase by some components of cigarette smoke

Inhibitory activity towards monoamine oxidase has been found in a solution of cigarette smoke. The inhibition was irreversible. When tissue slices of rat lung were incubated in the cigarette smoke solution or alternatively, exposed directly to cigarette smoke, monoamine oxidase activities were reduced drastically. Similarly, human saliva after cigarette smoking also exhibits considerable MAO inhibitory activity. When the amine substrates p-tyramine, serotonin and beta-phenylethylamine were incubated with the cigarette smoke solution, lipophilic adducts were formed non-enzymatically. The irreversible inhibition of MAO by cigarette smoke may well be related to the low platelet MAO associated with cigarette smokers as previously reported. The implication of such cigarette smoke-caused reduction of MAO activity in relation to Parkinsonism is discussed.     

Whole Cigarette Smoke Increased the Expression of TLRs,HBDs, and Proinflammory Cytokines by Human Gingival Epithelial Cells through Different Signaling Pathways

The gingival epithelium is becoming known as a regulator of the oral innate immune responses to a variety of insults such as bacteria and chemicals, including those chemicals found in cigarette smoke. We investigated the effects of whole cigarette smoke on cell-surface-expressed Toll-like receptors (TLR)-2, −4 and −6, human β-defensin (HBD) and proinflammatory cytokine expression and production in primary human gingival epithelial cells. Whole cigarette smoke was shown to increase TLR2, TLR4 and TLR6 expression. Cigarette smoke led to ERK1/2, p38 and JNK phosphorylation in conjunction with nuclear factor-κB (NFκB) translocation into the nucleus. TLR expression following cigarette smoke exposure was down regulated by the use of ERK1/2, p38, JNK MAP kinases, and NFκB inhibitors, suggesting the involvement of these signaling pathways in the cellular response against cigarette smoke. Cigarette smoke also promoted HBD2, HBD3, IL-1β, and IL-6 expression through the ERK1/2 and NFκB pathways. Interestingly, the modulation of TLR, HBD, and cytokine expression was maintained long after the gingival epithelial cells were exposed to smoke. By promoting TLR, HBDs, and proinflammatory cytokine expression and production, cigarette smoke may contribute to innate immunity dysregulation, which may have a negative effect on human health.     

Cigarette smoke ventilation decreases prostaglandin inactivation in rat and hamster lungs

The effects of cigarette smoke on the metabolism of exogenous PGE₂ and PGF_2α were investigated in isolated rat and hamster lungs. When isolated lungs from animals were ventilated with cigarette smoke during pulmonary infusion of 100 nmol of PGE₂ or PGF_2α, the amounts of the 15-keto-metabolites in the perfusion effluent were decreased. Pre-exposure of animals to cigarette smoke daily for 3 weeks did not change the metabolism of PGE₂ when the lungs were ventilated with air. Cigarette smoke ventilation of lungs from pre-exposed animals caused, however, a similar decrease in the metabolism of PGE₂ as in animals not previously exposed to smoke. After pulmonary injection of 10 nmol of ¹⁴C-PGE₂ the radioactivity appeared more rapidly in the effluent during cigarette smoke ventilation suggesting inhibition of the PGE₂ uptake mechanism. In rat lungs pulmonary vascular pressor responses to PGE₂ and PGF_2α were inhibited by smoke ventilation.     

The involvement of serotonin metabolism in cigarette smoke-induced oxidative stress in rat lung in vivo

Abstract

Recently, we have reported the dysregulation of circulating serotonin (5-hydroxytryptamine, 5-HT) homeostasis in patients with chronic obstructive pulmonary disease (COPD). An increase in metabolism of 5-HT has been reported to induce oxidative stress via monoamine oxidase (MAO)-dependent pathway. The present study aimed at investigating the effect of cigarette smoke exposure on the systemic circulation and local airway 5-HT levels as well as MAO-mediated oxidative pathway using a cigarette smoke-exposed rat model. Male Sprague-Dawley rats (150–200 g) were exposed to either sham air or 4% (v/v, smoke/air) cigarette smoke for 1 hour daily for 56 consecutive days. Sera, bronchoalveolar larvage (BAL) and lung tissues were collected 24 hours after the last exposure. We found a significant reduction in the reduced glutathione (rGSH) and an elevation in advanced oxidation protein products (AOPP), a protein oxidation marker, in the lung of cigarette smoke-exposed group (p?<?0.05). A significant increase in 5-HT was found in serum (p?<?0.05), but not in the BAL or lung, after cigarette smoke exposure. MAO-A activity was significantly elevated in the lung of cigarette smoke-exposed group (p?<?0.05). Furthermore, increased superoxide anion levels were found in lung homogenates of cigarette smoke-exposed rats after incubation with 5-HT (p?<?0.05), which was positively associated with the increase in MAO-A activity (r?=?0.639, p?<?0.05). Our findings supported the presence of GSH disruption and protein oxidation in the lung after cigarette smoke exposure. The metabolism of 5-HT by MAO-A in the lung enhanced cigarette smoke-induced superoxides, which might contribute to the pathogenesis of COPD.     

Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle

Cigarette smoke contributes to or exacerbates airway diseases such as asthma and COPD, where airway hyperresponsiveness and airway smooth muscle (ASM) proliferation are key features. While factors such as inflammation contribute to asthma in part by enhancing agonist-induced intracellular Ca²⁺ ([Ca²⁺]i) responses of ASM, the mechanisms by which cigarette smoke affect ASM are still under investigation. In the present study, we tested the hypothesis that cigarette smoke enhances the expression and function of Ca²⁺ regulatory proteins leading to increased store operated Ca²⁺ entry (SOCE) and cell proliferation. Using isolated human ASM (hASM) cells, incubated in the presence and absence cigarette smoke extract (CSE) we determined ([Ca²⁺]i) responses and expression of relevant proteins as well as ASM proliferation, reactive oxidant species (ROS) and cytokine generation. CSE enhanced [Ca²⁺]i responses to agonist and SOCE: effects mediated by increased expression of TRPC3, CD38, STIM1, and/or Orai1, evident by attenuation of CSE effects when siRNAs against these proteins were used, particularly Orai1. CSE also increased hASM ROS generation and cytokine secretion. In addition, we found in the airways of patients with long-term smoking history, TRPC3 and CD38 expression were significantly increased compared to life-long never-smokers, supporting the role of these proteins in smoking effects. Finally, CSE enhanced hASM proliferation, an effect confirmed by upregulation of PCNA and Cyclin E. These results support a critical role for Ca²⁺ regulatory proteins and enhanced SOCE to alter airway structure and function in smoking-related airway disease.     

The effect of curcumin in the ectonucleotidases and acetylcholinesterase activities in synaptosomes from the cerebral cortex of cigarette smoke-exposed rats

With the evidence that curcumin may be a potent neuroprotective agent and that cigarette smoke is associated with a decline in the cognitive performance as our bases, we investigated the activities of Ecto‐Nucleoside Triphosphate Diphosphohydrolase (NTPDase), 5'‐nucleotidase and acetylcholinesterase (AChE) in cerebral cortex synaptosomes from cigarette smoke‐exposed rats treated with curcumin (Cur). The experimental procedures entailed two sets of experiments. In the first set, the groups were vehicle, Cur 12·5, 25 and 50 mg·kg^–1; those in the second set were vehicle, smoke, smoke and Cur 12·5, 25 and 50 mg·kg^–1. Curcumin prevented the increased NTPDase, 5'‐nucleotidase and AChE activities caused by smoke exposure. We suggest that treatment with Cur was protective because the decrease of ATP and acetylcholine (ACh) concentrations is responsible for cognitive impairment, and both ATP and ACh have key roles in neurotransmission. Copyright © 2011 John Wiley & Sons, Ltd.     

Selenium and Vitamin E Modulates Cigarette Smoke Exposure-Induced Oxidative Stress in Blood of Rats

Cigarette smoke contains about 5,000 chemicals that include organic and metallic compounds. The current study was undertaken to investigate the effects of selenium and vitamin E on oxidative stress-induced damage in rats exposed to cigarette smoke. Forty male rats were equally divided into four groups. The first and second groups were used as control and cigarette smoke groups, respectively. Selenium was administered to rats constituting the third group for 27 days. The Se and vitamin E combination was given to animals in fourth group for 27 days. All groups except the control, were exposed to cigarette smoke starting at the third day of the experiment and continuing for 27 days. The blood samples from all groups were taken at the end of 27 days. Plasma lipid peroxidation, triacylglycerol, and total cholesterol levels were higher in the cigarette smoke group than in the control, although erythrocytic superoxide dismutase and glutathione peroxidase activities were lower in the cigarette smoke group than in the control. The plasma lipid peroxidation, triacylglycerol, and total cholesterol levels were lower in cigarette smoke+Se+VE group than in the cigarette smoke group, although erythrocytic superoxide dismutase activity and glutathione peroxidase activity in selenium and vitamin E-administered groups were higher than in the exposed to cigarette smoke group. High-density lipoprotein-cholesterol level was not affect by selenium and vitamin E administrations. In conclusion, selenium and vitamin E seem to have protective effects on the cigarette smoke-induced blood toxicity by supporting the enzymatic antioxidant redox systems.     

A Rat Model of Cigarette Smoke Abuse Liability

We sought to develop a rat model of cigarette smoke exposure (CSE) that created cotinine serum levels comparable to those of smokers and induced conditioned place preference (CPP) suggestive of cigarette smoke abuse liability. Rats were exposed to sidestream cigarette smoke delivered semicontinuously for 2 periods of 20 (group S20), 40 (group S40), or 60 (group S60) min daily for 12 wk. Serum cotinine concentration in blood samples was determined at 1 and 20 h after CSE. A biased (black versus white chamber) CPP paradigm was used. In the high CSE group (group S60), serum cotinine at 1 h (250 to 300 ng/mL) was comparable to average cotinine levels reported for addicted smokers (around 300 ng/mL). Cotinine levels at 20 h after CSE were higher than the smoker–nonsmoker cut-off value (greater than 14 ng/mL) in all smoking groups, with the S60 group having the highest levels. All rats preferred the black chamber to the white chamber during the preexposure CPP test. The time spent in the white chamber was increased compared with 0-wk values in group S40 at 8 wk, group S60 at 4 and 8 wk, and the control group at 4 and 8 wk but not at 12 wk; however, the shift in CPP was significantly higher at 8 wk in group S60 compared with other groups. In conclusion, interrupted 2-h daily CSE for 8 wk induced serum cotinine levels in rats comparable to those of smokers and induced CPP suggestive of cigarette smoke abuse liability.Abbreviations: CPP, conditioned place preference; CSE, cigarette smoke exposureThe devastating consequences of smoking on health have been studied extensively in numerous clinical and animal studies over time. This chronic habit leads to dependence on tobacco smoke, with nicotine, a main active ingredient of tobacco products, being recognized as the basic addictive substance.³²The known health benefits of smoking cessation motivate smokers to quit tobacco use. However, unaided efforts usually are unsuccessful, resulting in smoking relapse. The fight against nicotine addiction may be undermined by potential weight gain after smoking cessation, potentially discouraging those attempting to quit smoking and contributing to relapse. During the past few years, research has been focused on 2 main areas of interest toward this direction: understanding the underlying biologic mechanisms related to nicotine addiction to effectively design therapeutic strategies to support those who wish to quit smoking and investigating the hormonal and molecular mechanisms responsible for weight gain after smoking cessation.So far, animal models used to study the consequences of smoking cessation involved the administration of nicotine as a sole agent until addiction was achieved.²³ However, nicotine-administration models do not completely represent the toxic and addictive effects of cigarette smoke, given that smoke contains more than 4000 chemicals whose actions or coactions have not been thoroughly evaluated yet.¹ Cigarette smoke exposure (CSE) animal models have been used in studies investigating the metabolic changes conferred by smoking^10-12 but not in those after its cessation. In toxicity studies, animals are exposed to tobacco smoke for various periods, which depend on the side effect under investigation.^18,25,27 Smoke exposure timetables usually do not involve weekends for practical reasons, and addiction of animals to tobacco smoke is not assessed in current models.In our opinion, an ideal animal model of cigarette smoke abuse liability suitable for the study of smoking cessation resembles the clinical situation in terms of chronic daily inhalation of cigarette smoke sufficient to attain blood nicotine levels comparable to those of smokers and in cessation of the CSE period after achieving tobacco smoke abuse liability. In the present project, we sought to establish such a model in rats by defining the daily timetable of CSE to induce serum levels of cotinine, nicotine''s major proximate metabolite, comparable to those of smokers and by determining the minimum total CSE period required to induce abuse liability to cigarette smoke. We assessed the CSE period by using a biased conditioned place preference (CPP) paradigm.⁸     

Continuous and Discontinuous Cigarette Smoke Exposure Differentially Affects Protective Th1 Immunity against Pulmonary Tuberculosis

Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of death due to a bacterial pathogen. Emerging epidemiologic evidence suggests that the leading risk factor associated with TB mortality is cigarette smoke exposure. Despite this, it remains poorly understood what is the effect of cigarette smoke exposure on anti-TB immunity and whether its potential detrimental effect can be reversed by cigarette smoking cessation. In our current study, we have investigated the impact of both continuous and discontinuous cigarette smoke exposure on the development of anti-mycobacterial type 1 immunity in murine models. We find that while continuous cigarette smoke exposure severely impairs type 1 immunity in the lung, a short-term smoking cessation allows rapid restoration of anti-mycobacterial immunity. The ability of continuous cigarette smoke exposure to dampen type 1 protective immunity is attributed locally to its affects on innate immune cells in the lung. Continuous cigarette smoke exposure locally, by not systemically, impairs APC accumulation and their production of TNF, IL-12, and RANTES, blunts the recruitment of CD4+IFN-γ+ T cells to the lung, and weakens the formation of granuloma. On the other hand, smoking cessation was found to help restore type 1 immunity by rapidly improving the functionality of lung APCs, enhancing the recruitment of CD4+IFN-γ+ T cells to the lung, and promoting the formation of granuloma. Our study for the first time demonstrates that continuous, but not discontinuous, cigarette smoke exposure severely impedes the lung expression of anti-TB Th1 immunity via inhibiting innate immune activation and lung T cell recruitment. Our findings thus suggest cigarette smoking cessation to be beneficial to the control of pulmonary TB.