Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: Development of tolerance using environmental antigens

Wang, Yufa; McCusker, Christine

doi:10.1016/j.jaci.2006.03.020

Cited by 70 publications

(67 citation statements)

References 51 publications

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“…Intrapulmonary LPS administration to mice has been shown to prevent experimental allergic asthma, associated with an absence of allergen-specific Th2 or Th1 cytokines, suggested to be anergy (55). Other studies have implicated Th1 responses, because of elevated expression of the transcription factor T-bet (56) or a requirement for IL-12 (32), and/or IL-10-producing CD4 + cell responses (34,57), in the inhibition of Th2-mediated allergic airway disease, depending on the timing of intrapulmonary LPS exposure in relation to disease onset or development. We aimed to characterize the CD4 T cell response associated with the TLR4-dependent inhibition of experimental allergic airway disease via the nasal mucosa by nasal Protollin administration, but found no induction of IFN-g mRNA in the NALT, or protein in CD4…”

Section: Discussionmentioning

confidence: 99%

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Shalaby

Nakada

et al. 2012

The Journal of Immunology

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Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2−/−, or Tlr4−/− BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges. Nasal application of Protollin or Protollin admixed with BPEx was sufficient to inhibit allergic lower airway disease with minimal collateral lung inflammation. Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4+Foxp3+ and CD4+Foxp3− T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs. Adoptive transfer of cervical LN CD4+ICOS+, but not CD4+ICOS−, cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia. Thus, our data indicate that expansion of resident ICOS-expressing CD4+ T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.

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Section: Discussionmentioning

confidence: 99%

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Shalaby

Nakada

et al. 2012

The Journal of Immunology

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“…Animal models have correlated high-dose LPS exposure with decreased allergen sensitization, whereas low levels of LPS seem to potentiate sensitization [31,32]. Wang et al [33] showed that intranasal exposure to LPS in neonatal mice protected from ovalbumin sensitization and resulted in increased regulatory T cell numbers. Further, it has been shown that TLR4 signaling is required for the development of antigenic tolerance in previously sensitized mice, but is not required for the development of sensitization [34].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Endotoxin Tolerance Protects against Cockroach Allergen-Induced Asthma-Like Inflammation in a Mouse Model

Natarajan

Kim²,

Bouchard³

et al. 2012

Int Arch Allergy Immunol

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Background: Compounds which activate the innate immune system, such as lipopolysaccharide, are significant components of ambient air, and extremely difficult to remove from the environment. It is currently unclear how prior inhalation of endotoxin affects allergen sensitization. We examined whether lung-specific endotoxin tolerance induction prior to sensitization can modulate the response to allergen. Methods: Endotoxin tolerance was induced by repeated intratracheal exposure to endotoxin. All mice were then sensitized and challenged by direct intratracheal instillation of cockroach allergen. Results: After allergen sensitization and challenge, endotoxin tolerant mice had significantly decreased airways hyperresponsiveness to methacholine challenge, which was confirmed by invasive lung function tests. Decreased goblet cell hyperplasia and mucus production were also found by histological assessment. Tolerant mice were protected from airway eosinophilia through the mechanism of reduced CCL11 and CCL24. Interestingly, endotoxin tolerant mice had only a modest reduction in cockroach-specific IgE; however, total IgE was significantly reduced. Conclusions: These data show that induction of endotoxin tolerance prior to sensitization protects against the hallmark features of asthma-like inflammation, and that transient modulation of innate immunity can have long-lasting effects on adaptive responses.

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“…Wang et al have demonstrated that prevention of airway allergy may be best achieved by specific exposure (LPS and allergen) of the airway mucosa early in life to environmental antigens potentially reflecting early mucosal tolerance 23 .…”

Section: Correlation Between Il-17 and Ifn-γmentioning

confidence: 99%

Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells

Schaub¹,

Liu

Höppler³

et al. 2009

Journal of Allergy and Clinical Immunology

388

300

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Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: Development of tolerance using environmental antigens

Cited by 70 publications

References 51 publications

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Pulmonary Endotoxin Tolerance Protects against Cockroach Allergen-Induced Asthma-Like Inflammation in a Mouse Model

Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells

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