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. 2014 Jun 1;192(11):5226-35.
doi: 10.4049/jimmunol.1302584. Epub 2014 Apr 21.

"V体育ios版" Cigarette smoke exposure exacerbates lung inflammation and compromises immunity to bacterial infection

Amit A Lugade  1 , Paul N Bogner  2 , Thomas H Thatcher  3 , Patricia J Sime  4 , Richard P Phipps  4 , Yasmin Thanavala  5
Affiliations

V体育安卓版 - Cigarette smoke exposure exacerbates lung inflammation and compromises immunity to bacterial infection

Amit A Lugade et al. J Immunol. .

Abstract

The detrimental impact of tobacco on human health is clearly recognized, and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease are susceptible to recurrent respiratory infections with pathogens, including nontypeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. Because mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study, to our knowledge, to investigate chronic infection and the generation of adaptive immune responses to NTHI after chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of Abs against outer-membrane lipoprotein P6, with impaired IgG1, IgG2a, and IgA class switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke-exposed mice exhibited a similar defect in the generation of adaptive immunity after immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes chronic obstructive pulmonary disease patients to recurrent infections, leading to exacerbations and contributing to mortality. VSports手机版.

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DISCLOSURES

The authors have no financial conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Cigarette smoke exposure exacerbates NTHI-mediated chronic respiratory inflammation. (A) C57BL/6J female mice were exposed for 4 weeks to cigarette smoke or air, followed by 8 weeks of NTHI (n=10 air + NTHI; n=8 cigarette smoke + NTHI). (B) H&E stained lung sections prepared after combined inflammatory insult were evaluated for the extent and severity of inflammation. Lymphocytic cuffs are present adjacent to vasculature (arrows) and airways (arrowheads). Bars represent 100 µm. (C) Consensus scores from two blinded non-consecutive sessions evaluating respiratory inflammation in peribronchial, pleural, and interstitial regions of the lung.
FIGURE 2
FIGURE 2
Cigarette smoke exposure modulates airway immune cell composition and cytokine profile. (A) Bronchoalveolar lavage (BAL) fluid was evaluated for the composition of immune cells accumulating within airways following 8 weeks of NTHI-mediated chronic respiratory inflammation (n=10 air + NTHI; n=8 cigarette smoke + NTHI). Frequency and number of neutrophils, macrophages, and lymphocytes was determined by Wright-Giemsa differential staining. (B) Concentration of cytokines in BAL fluid was determined by ELISA. Line represents mean; *p<0.05, **p<0.01, ***p<0.001 two-tailed unpaired t-test.
FIGURE 3
FIGURE 3
P6-specific T cells with Th17 signature are elevated in cigarette smoke exposed mice. Single-cell suspensions of (A) lung lymphocytes and (B) splenocytes were isolated from air or cigarette smoke exposed mice and incubated with P641–55 peptide pulsed APCs. Amount of cytokine secreted was measured by ELISA and frequency of cytokine secreting T cells was measured by ELISPOT. Line represents mean; *p<0.05, **p<0.01, ***p<0.001 two-tailed unpaired t-test.
FIGURE 4
FIGURE 4
Frequency of antibody-secreting NTHI-specific cells is decreased in cigarette smoke exposed mice. B cell ELISPOTs were performed to quantify frequency of P6-specific IgG1- and IgG2a-secreting cells from bone marrow (top row) and spleens (bottom row) of air or cigarette smoke exposed mice. Line represents mean; *p<0.05, **p<0.01 two-tailed unpaired t-test.
FIGURE 5
FIGURE 5
Cigarette smoke exposure modulates accumulation of anti-P6 Ig in airways and serum. Levels of anti-P6 Ig were measured in (A) BAL fluid and (B) serum from air or cigarette smoke exposed mice receiving 8 weeks of chronic NTHI exposure. OD values at 405 nm for (C) BAL fluid dilutions at 10−2.6 (1:400) and (D) sera dilutions at 10−3.2 (1:1600) were analyzed for levels of P6-specific IgA, IgG1, IgG2a, and IgG2b. Line represents mean; *p<0.05, **p<0.01 two-tailed unpaired t-test.
FIGURE 6
FIGURE 6
Immunization efficacy is compromised in cigarette smoke exposed mice. (A) C57BL/6 female mice were immunized i.p. with 40 µg lipoprotein P6 from NTHI outer membrane after receiving 4 weeks of air or cigarette smoke exposure (n=10 air + NTHI; n=9 cigarette smoke + NTHI). Vaccination efficacy was measured 16 weeks after i.p. immunization. Levels of anti-P6 Ig were measured from (B) weekly serum samples and (C) BAL fluid obtained at termination. (D) OD values at 405 nm for sera were determined for levels of P6-specific IgG1 and IgG2a. (E) OD values at 405 nm for BAL fluid was analyzed for levels of P6-specific IgA and IgG2b. Mean ± SD; †p<0.05 AUC Kruskal-Wallis rank test. Line represents mean; *p<0.05 two-tailed unpaired t-test.
FIGURE 7
FIGURE 7
P6 immunization in cigarette smoke exposed mice marginally mitigates acute NTHI-mediated inflammation. (A) Hallmarks of acute inflammation were measured in air or cigarette smoke exposed mice 16 weeks after P6 immunization or sham immunization. Kinetics of acute inflammation was evaluated at baseline and 4 or 24 hrs post NTHI challenge. (B) Rate of NTHI clearance in the lung was measured by colony-plating assay. (C) Accumulation of neutrophils in BAL determined by Wright-Giemsa differential staining. (D-G) Concentration of albumin and pro-inflammatory cytokines in BAL fluid determined by ELISA. n=3 mice per group per time point; mean ± SD; p<0.01 2-way ANOVA, *p<0.05 Bonferroni post-test comparison of air vs cigarette smoke.
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References

    1. Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet. 2004;364:709–721. - V体育官网 - PubMed
    1. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004;350:2645–2653. - PubMed
    1. Carolan BJ, Sutherland ER. Clinical phenotypes of chronic obstructive pulmonary disease and asthma: recent advances. J. Allergy Clin. Immunol. 2013;131:627–634. - PubMed
    1. Spencer P, Krieger B. The differentiation of chronic obstructive pulmonary disease from asthma: a review of current diagnostic and treatment recommendations. Open. Nurs. J. 2013;7:29–34. - PMC - PubMed
    1. Eisner MD, Balmes J, Katz PP, Trupin L, Yelin EH, Blanc PD. Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease. Environ. Health. 2005;4:7. - V体育ios版 - PMC - PubMed

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