Live Attenuated Influenza Virus (LAIV) induces different mucosal T cell function in nonsmokers and smokers

Horvath, Katherine M.; Brighton, Luisa E.; Herbst, M; Noah, Terry L.; Jaspers, Ilona

doi:10.1016/j.clim.2011.12.013

Cited by 27 publications

(28 citation statements)

References 21 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies demonstrated that smokers inoculated with liveattenuated influenza virus (LAIV) vaccine had reduced cytotoxic NK cells and markers of activated NK cells in their nasal lavage (17). In a similar study, we demonstrated that LAIVinduced recruitment of ␥/␦ T cells into the nasal mucosa is impaired in smokers (16). Thus smoking-induced gene silencing of ULBP3 in NECs could lead to decreased NK cell and ␥/␦ T cell function in the nasal mucosa in the context of viral infection and result in impaired ability to recognize and eliminate virus-infected host cells.…”

Section: Discussionsupporting

confidence: 53%

DNA methylation in nasal epithelial cells from smokers: identification of ULBP3-related effects

Rager¹,

Bauer²,

Müller

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

-We previously demonstrated that, in nasal epithelial cells (NECs) from smokers, methylation of an antiviral gene was associated with impaired antiviral defense responses. To expand these findings and better understand biological mechanisms underlying cigarette smoke (CS)-induced modifications of host defense responses, we aimed to compare DNA methylation of genes that may play a role in antiviral response. We used a two-tiered analytical approach, where we first implemented a genome-wide strategy. NECs from smokers differed in the methylation levels of 390 genes, the majority (84%) of which showed decreased methylation in smokers. Secondly, we generated an a priori set of 161 antiviral response-related genes, of which five were differentially methylated in NEC from smokers (CCL2, FDPS, GSK3B, SOCS3, and ULBP3). Assessing these genes at the systems biology level revealed a protein interaction network associated with CS-induced epigenetic modifications involving SOCS3 and ULBP3 signaling, among others. Subsequent confirmation studies focused on SOCS3 and ULBP3, which were hypomethylated and hypermethylated, respectively. Expression of SOCS3 was increased, whereas ULBP3 expression was decreased in NECs from smokers. Addition of the demethylating agent 5-Aza-2-deoxycytidine enhanced ULBP3 expression in NECs from smokers. Furthermore, infection of differentiated NECs with influenza virus resulted in significantly lower levels of ULBP3 in cells from smokers. Taken together, our findings show that genomic DNA methylation profiles are altered in NECs from smokers and that these changes are associated with decreased antiviral host defense responses, indicating that epigenenic dysregulation of genes such as SOCS3 and ULBP3 likely impacts immune responses in the epithelium.

show abstract

Section: Discussionsupporting

confidence: 53%

DNA methylation in nasal epithelial cells from smokers: identification of ULBP3-related effects

Rager¹,

Bauer²,

Müller

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

“…We and others have shown that cigarette smoking modifies mucosal host defense, yet the specific mechanisms mediating this effect remain unclear (19,20,22,36). A hallmark of cigarette smoking is a shift in the protease/antiprotease balance in favor of protease expression and activity (1,28,53).…”

Section: Discussionmentioning

confidence: 99%

Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in smokers

Meyer

Bauer

Letang

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

A hallmark of cigarette smoking is a shift in the protease/antiprotease balance, in favor of protease activity. However, it has recently been shown that smokers have increased expression of a key antiprotease, secretory leukoprotease inhibitor (SLPI), yet the mechanisms involved in SLPI transcriptional regulation and functional activity of SLPI remain unclear. We examined SLPI mRNA and protein secretion in differentiated nasal epithelial cells (NECs) and nasal lavage fluid (NLF) from nonsmokers and smokers and demonstrated that SLPI expression is increased in NECs and NLF from smokers. Transcriptional regulation of SLPI expression was confirmed using SLPI promoter reporter assays followed by chromatin immunoprecipitation. The role of STAT1 in regulating SLPI expression was further elucidated using WT and stat1(-/-) mice. Our data demonstrate that STAT1 regulates SLPI transcription in epithelial cells and slpi protein in the lungs of mice. Additionally, we reveal that NECs from smokers have increased STAT1 mRNA/protein expression. Finally, we demonstrate that SLPI contained in the nasal mucosa of smokers is proteolytically cleaved but retains functional activity against neutrophil elastase. These results demonstrate that smoking enhances expression of SLPI in NECs in vitro and in vivo, and that this response is regulated by STAT1. In addition, despite posttranslational cleavage of SLPI, antiprotease activity against neutrophil elastase is enhanced in smokers. Together, our findings show that SLPI regulation and activity is altered in the nasal mucosa of smokers, which could have broad implications in the context of respiratory inflammation and infection.

show abstract

“…Moreover, it has been reported that the persistence of immunity to hepatitis B in cigarette smokers was lower than nonsmokers [19]. It has been recently reported that the immune response (within the nasal mucosa) to attenuated influenza virus vaccine were suppressed in smokers as compared to nonsmokers [20]. Furthermore, it has been reported that cigarette smokers are susceptible to infection and sepsis [21].…”

Section: Figure 1: Distribution Of Subjects According To Anti-tetanusmentioning

confidence: 99%

Lower immunity to tetanus in cigarette smoker subjects

Jafarzadeh

Shabani

Hassanabadi

et al. 2012

JOHE

View full text Add to dashboard Cite

Received: February 2013, Accepted: October 2013 Background: Cigarette smoking has been linked with the suppression of immune responses and increased susceptibility to numerous infections in humans. Tetanus is also a major public health problem in many countries. The aim of the present study was to evaluate the serum levels of antitetanus toxin antibodies in cigarette smoking and healthy non-smoking people. Materials and Methods: A total of 100 cigarette smokers and 100 age-matched healthy nonsmoker individuals were enrolled in this descriptive study. A blood sample was collected from each participant. The samples were tested for the levels of anti-tetanus toxin antibodies by use of enzyme linked immunosorbent assay. Results: The seroprotective rate of anti-tetanus toxin antibodies in non-smoking group (99%) was significantly higher than that observed in cigarette smoking group (78%, P<0.0001). The mean titer of anti-tetanus toxin antibodies in non-smoking group (5.32± 0.26 IU/ml) was also significantly higher than that in smoker subjects (1.03 ± 0.16 IU/ml; P<0.0001). The mean titer of anti-tetanus toxin antibodies in individuals with smoking duration >10 years was significantly lower than that among smokers with smoking duration ≤10 years (0.59 ± 0.12 IU/ml vs 1.98 ± 0.41 IU/ml; P<0.001). The seroprotection rate was also significantly lower in persons with smoking duration >10 years in comparison to smokers with smoking duration ≤10 years (72.1% vs 90.6%; P=0.037). The mean titer of anti-tetanus toxin antibodies in individuals with daily smoking >10 cigarettes was also significantly lower in comparison to smokers with daily smoking ≤10 cigarettes (0.68 ± 0.15 IU/ml vs 1.63 ± 0.36 IU/ml; P<0.001). Conclusion: These results showed lower levels of anti-tetanus toxin antibodies in cigarette smokers which represents cigarette smoking as a risk factor for susceptibility to tetanus. A negative association was also observed between the immunity to tetanus and smoking burden.

show abstract

Live Attenuated Influenza Virus (LAIV) induces different mucosal T cell function in nonsmokers and smokers

Cited by 27 publications

References 21 publications

DNA methylation in nasal epithelial cells from smokers: identification of ULBP3-related effects

DNA methylation in nasal epithelial cells from smokers: identification of ULBP3-related effects

Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in smokers

Lower immunity to tetanus in cigarette smoker subjects

Contact Info

Product

Resources

About