Immunoregulatory and immunostimulatory responses of bacterial lysates in respiratory infections and asthma

Kearney, Sean Christopher; Dziekiewicz, Marcin; Feleszko, Wojciech

doi:10.1016/j.anai.2015.02.008

Cited by 102 publications

(119 citation statements)

References 64 publications

(90 reference statements)

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“…Dendritic cells (DCs) play an important role in immunity and display Toll-like receptors (TLRs), which are pattern recognition receptors for pathogenic microbes [8][9][10]. Multiple TLRs participate in allergic inflammation, including TLR2, TLR4, and TLR9.…”

mentioning

confidence: 99%

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Huang²,

Zhu

et al. 2018

Int Arch Allergy Immunol

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Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam₃CSK₄. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.

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confidence: 99%

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Huang²,

Zhu

et al. 2018

Int Arch Allergy Immunol

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“…These findings support the conclusion that most of the bacterial DNA isolated from lung tissue derives from extracellular, dead, or phagocytosed/non-viable organisms. Such DNA could nevertheless be biologically relevant as CpG motifs present in bacterial DNA can activate the innate immune system via Toll-like receptor 9 [42;43]. Similarly, macrophages, bronchial and alveolar epithelial cells express pathogen recognition receptors that are stimulated by motifs expressed by even non-viable bacteria [44;45].…”

Section: Discussionmentioning

confidence: 99%

Three distinct pneumotypes characterize the microbiome of the lung in BALB/cJ mice

Scheiermann

Klinman

2017

PLoS ONE

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Bacteria can rarely be isolated from normal healthy lungs using conventional culture techniques, supporting the traditional belief that the lungs are sterile. Yet recent studies using next generation sequencing report that bacterial DNA commonly found in the upper respiratory tract (URT) is present at lower levels in the lungs. Interpretation of that finding is complicated by the technical limitations and potential for contamination introduced when dealing with low biomass samples. The current work sought to overcome those limitations to clarify the number, type and source of bacteria present in the lungs of normal mice. Results showed that the oral microbiome is diverse and highly conserved whereas murine lung samples fall into three distinct patterns. 33% of the samples were sterile, as they lacked culturable bacteria and their bacterial DNA content did not differ from background. 9% of samples contained comparatively higher amounts of bacterial DNA whose composition mimicked that detected in the URT. A final group (58%) contained smaller amounts of microbial DNA whose composition was correlating to that of rodent chow and cage bedding, likely acquired by inspiration of food and bedding fragments. By analyzing each sample independently rather than working with group averages, this work eliminated the bias introduced by aspiration-contaminated samples to establish that three distinct microbiome pneumotypes are present in normal murine lungs.

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“…Bacterial lysates, immunoregulatory cellular extracts that have been found to reduce allergic airway inflammation in mouse models, may be an effective alternative [95–97]. The most studied bacterial lysate is OM-85 BV, which contains extracts derived from 8 bacterial species: Staphylococcus aureus, Streptococcus species , Klebsiella species , Neisseria catarrhalis and Haemophilus influenzae .…”

Section: Potential Benefit Of Immunostimulant Microbial Exposuresmentioning

confidence: 99%

“…The most studied bacterial lysate is OM-85 BV, which contains extracts derived from 8 bacterial species: Staphylococcus aureus, Streptococcus species , Klebsiella species , Neisseria catarrhalis and Haemophilus influenzae . Several trials, though generally small and with significant heterogeneity, have demonstrated that bacterial lysate treatment reduces recurrent respiratory tract infections in adults and children [98–101], and OM-85 BV has been used for decades for this indication in Europe [95]. A small clinical trial of 75 children between ages 1 and 6 with recurrent wheeze found a nearly 40% reduction in number of wheezing attacks and a reduction in duration of wheezing attacks over one year of follow-up in those randomized to OM-85 BV treatment [102].…”

Section: Potential Benefit Of Immunostimulant Microbial Exposuresmentioning

confidence: 99%

Strategies to alter the natural history of childhood asthma

Lee-Sarwar

Bacharier

Litonjua

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Asthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findings Variations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short- and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. Summary The identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation.

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Immunoregulatory and immunostimulatory responses of bacterial lysates in respiratory infections and asthma

Cited by 102 publications

References 64 publications

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Three distinct pneumotypes characterize the microbiome of the lung in BALB/cJ mice

Strategies to alter the natural history of childhood asthma

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