TLR2/6 stimulation of the rat lung: effects on lymphocyte subsets, natural killer cells and dendritic cells in different parts of the air‐conducting compartments and at different ages

Pabst, Reinhard; Durak, Deniz; Roos, Anna Karin; Lührmann, Anke; Tschernig, Thomas

doi:10.1111/j.1365-2567.2008.02886.x

Cited by 22 publications

(15 citation statements)

References 37 publications

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“…Other studies reported differences in the leukocyte influx into the lung interstitium between rats of different ages after the intratracheal application of MALP-2. 72,73 Taken together with clinical observations, these findings caution against generalizations of the immune responses between different age groups and suggest that susceptibility to develop iBALT is heightened in early life. However, the molecular pathways that underpin this phenomenon remain undefined.…”

Section: Age Dependencymentioning

confidence: 70%

Regulation of inducible BALT formation and contribution to immunity and pathology

2010

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Inducible bronchus-associated lymphoid tissue (iBALT) is an organized tertiary lymphoid structure that is not pre-programmed but develops in response to infection or under chronic inflammatory conditions. Emerging research has shown that iBALT provides a niche for T-cell priming and B-cell education to assist in the clearance of infectious agents, highlighting the prospect that iBALT may be engineered and harnessed to enhance protective immunity against respiratory pathogens. Although iBALT formation is associated with several canonical factors of secondary lymphoid organogenesis such as lymphotoxin-α and the homeostatic chemokines, CXCL13, CCL19, and CCL21, these cytokines are not mandatory for its formation, even though they influence its organization and function. Similarly, lymphoid tissue-inducer cells are not a requisite of iBALT formation. In contrast, dendritic cells are emerging as pivotal players required to form and sustain the presence of iBALT. Regulatory T cells appear to be able to attenuate the development of iBALT, although the underlying mechanisms remain ill-defined. In this review, we discuss facets unique to iBALT induction, the cellular subsets, and molecular cues that govern this process, and the contribution of this ectopic structure toward the generation of immune responses in the pulmonary compartment.

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Section: Age Dependencymentioning

confidence: 70%

Regulation of inducible BALT formation and contribution to immunity and pathology

2010

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“…Repeated inhalation of heat-killed P. aeruginosa in mice (31) or applying the TLR 2/6 agonist MALP-2 in rats (52,53) increased and activated BALT. Agents known to induce or inhibit BALT was summarized in Table 1.…”

Section: The Two-step Concept To Take Advantage Of Balt In Mucosal Vamentioning

confidence: 99%

Bronchus-Associated Lymphoid Tissue

Pabst

Tschernig²

2010

Am J Respir Cell Mol Biol

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An accumulation of lymphoid cells with a typical localization of B lymphocytes preferentially in a follicle and T lymphocytes, more peripherally around high endothelial venules in the wall of bronchi, is called bronchus-associated lymphoid tissue (BALT). A further structural component is a cap-like accumulation of lymphoid cells partly bulging into the lumen of the bronchus, called the dome area. The epithelium covering the dome lacks goblet cells, is infiltrated by lymphocytes, and contains cells specialized for antigen uptake-M cells. BALT is not present in all species and age groups and can be classified as a tertiary lymphoid organ. A hypothesis is proposed for a two-step vaccination protocol: first, BALT is induced and activated, and second, an antigen-the vaccine-is applied locally. BALT is part of the integrated mucosal-associated lymphoid tissue system.

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“…In addition, MALP-2 promoted airway neutrophilia and the production of the IL-12 p70 subunit [54]. Interestingly, it has been shown that MALP-2 is able to activate neutrophils to produce chemokines and stimulate T cell, B cell and natural killer cell accumulation in the lung of treated mice, with more potency in male and adult subjects [55]. Bisacyloxypropylcysteine polyethylene glycol (BPPcysMPEG)is a derivate of MALP-2 that is also capable of stimulating TLR2/6 and also has the ability to abrogate Th2 response and airway eosinophilia in murine asthma models [56].…”

Section: Tlr1 2 6 and 10mentioning

confidence: 99%

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

Aryan

Holgate

Radzioch

et al. 2014

Int Arch Allergy Immunol

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Toll-like receptors (TLR) belong to a large family of pattern recognition receptors known as the ancient ‘gatekeepers' of the immune system. TLRs are located at the first line of defense against invading pathogens as well as aeroallergens, making them interesting targets to modulate the natural history of respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or prophylactic preparations useful for asthma/allergic rhinitis (AR) patients. MPL® (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9 agonist, show strong immunogenicity effects that make them appropriate adjuvants for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific allergen immunotherapy, currently the only available ‘curative' treatment for respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so far reported with such compounds targeting TLRs, with the most common adverse effects being transient and local irritation (e.g. redness, swelling and pruritus). Many other compounds that target TLRs have been found to suppress airway inflammation, eosinophilia and airway hyper-responsiveness in various animal models of allergic inflammation. Indeed, in the future a wide variability of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are likely to emerge.

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TLR2/6 stimulation of the rat lung: effects on lymphocyte subsets, natural killer cells and dendritic cells in different parts of the air‐conducting compartments and at different ages

Cited by 22 publications

References 37 publications

Regulation of inducible BALT formation and contribution to immunity and pathology

Regulation of inducible BALT formation and contribution to immunity and pathology

Bronchus-Associated Lymphoid Tissue

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

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