Short cigarette smoke exposure facilitates sensitisation and asthma development in mice.

Epidemiological studies indicate that cigarette smoke exposure is a risk factor for increased sensitisation and asthma development. The aim of this study was to examine the impact of cigarette smoke on sensitisation and allergic airway inflammation in response to a low dose of house dust mite (HDM), and to obtain potential mechanistic insights. Mice were exposed to low doses of HDM extract combined with air or cigarette smoke exposure, either during allergen sensitisation or during the development of allergic airway disease. Mice concomitantly exposed to low-dose HDM, combined with cigarette smoke for 3 weeks, demonstrated an asthmatic phenotype with significantly increased airway eosinophilia, goblet cell metaplasia, airway hyperresponsiveness and a rise in HDM-specific serum immunoglobulin G1, compared to sole HDM or cigarette smoke exposure. In addition, short cigarette smoke inhalation, during the initial contact with HDM allergens, was sufficient to facilitate sensitisation and development of a complete asthmatic phenotype after rechallenge with HDM. Mechanistically, short cigarette smoke exposure amplified dendritic cell-mediated transport of fluorescein isothiocyanate-labelled HDM allergens to the intrathoracic lymph nodes and generated a local T-helper cell type 2 response. Short cigarette smoke exposure is sufficient to facilitate allergic sensitisation and the development of low-dose HDM-induced allergic asthma, possibly by affecting dendritic cell function.

Exacerbation of cigarette smoke-induced pulmonary inflammation by Staphylococcus aureus enterotoxin B in mice.

BACKGROUND: Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation. OBJECTIVE: To study the effect of Staphylococcus aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD. METHODS: C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 µg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected. RESULTS: Combined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8+ T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs. CONCLUSIONS: Combined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that Staphylococcus aureus could influence the pathogenesis of COPD.

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation.

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed.

Concomitant inhalation of cigarette smoke and aerosolized protein activates airway dendritic cells and induces allergic airway inflammation in a TLR-independent way.

Cigarette smoking is associated with the development of allergic asthma. In mice, exposure to cigarette smoke sensitizes the airways toward coinhaled OVA, leading to OVA-specific allergic inflammation. Pulmonary dendritic cells (DCs) are professional APCs involved in immunosurveillance and implicated in the induction of allergic responses in lung. We investigated the effects of smoking on some of the key features of pulmonary DC biology, including trafficking dynamics and cellular activation status in different lung compartments. We found that cigarette smoke inhalation greatly amplified DC-mediated transport of inhaled Ags to mediastinal lymph nodes, a finding supported by the up-regulation of CCR7 on airway DCs. Pulmonary plasmacytoid DCs, which have been involved in inhalational tolerance, were reduced in number after smoke exposure. In addition, combined exposure to cigarette smoke and OVA aerosol increased surface expression of MHC class II, CD86, and PDL2 on airway DCs, while ICOSL was strongly down-regulated. Although inhaled endotoxins, which are also present in cigarette smoke, have been shown to act as DC activators and Th2-skewing sensitizers, TLR4-deficient and MyD88 knockout mice did not show impaired eosinophilic airway inflammation after concomitant exposure to cigarette smoke and OVA. From these data, we conclude that cigarette smoke activates the pulmonary DC network in a pattern that favors allergic airway sensitization toward coinhaled inert protein. The TLR independency of this phenomenon suggests that alternative immunological adjuvants are present in cigarette smoke.