Antigen Presentation by Local Macrophages Promotes Nonallergic Airway Responses in Sensitized Mice

Pynaert, Gwenda; Rottiers, Pieter; Haegeman, Anuschka; Sehra, Sarita; Belle, Tom Van; Korf, Hannelie; Grooten, Johan

doi:10.1165/rcmb.2003-0014oc

Cited by 14 publications

(11 citation statements)

References 34 publications

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“…Depletion of alveolar Mw increased the IgE responses [18] and adoptive transfer of alveolar Mw abrogated AHR [19]. Recently, PYNAERT et al [27] showed that spleen Mw, loaded with OVA and intratracheal-administered, suppressed airway eosinophilia, probably, by inducing a Th1-mediated counter regulation in the lung [8,27]. In contrast, in the present study evidence was obtained for an indirect mechanism by which Mw can suppress anti-inflammatory responses in the lung.…”

Section: Discussioncontrasting

confidence: 58%

Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model

Vissers

Esch²,

Hofman³

et al. 2005

Eur Respir J

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Increasing evidence suggests that macrophages (Mw) play a crucial downregulatory role in the initiation and progression of allergic asthma. Recently, the current authors demonstrated that ovalbumin (OVA)-loaded Mw (OVA-Mw) suppress subsequent OVA-induced airway manifestations of asthma and that this effect could be potentiated upon selective activation. In the present study, the authors further delineated the underlying pathway by which Mw exert this immunosuppressive effect.To examine the migration of OVA-Mw, cells were labelled with 59chloromethylfluorescein diacetate (CMFDA) and were administered (i.v.) into OVA-sensitised BALB/c mice. After 20 h, the relevant organs were dissected and analysed using fluorescent microscopy. Allergen-specificity was investigated by treating OVA-sensitised mice with keyhole limpet haemocyanin (KLH)-Mw activated with immunostimulatory sequence oligodeoxynucleotide (ISS-ODN). By lengthening the period between treatment and challenge to 4 weeks it was examined whether OVA-Mw exerted an immunosuppressive memory response.Strikingly, CMFDA-labelled Mw were not trapped in the lungs, but migrated to the spleen. ISS-ODN-stimulated KLH-Mw failed to suppress OVA-induced airway manifestations of asthma. Moreover, treatment with ISS-ODN-stimulated OVA-Mw was still effective after lengthening the period between treatment and challenge.These data demonstrate that allergen-loaded macrophages can induce an indirect immunosuppressive response that is allergen-specific and long lasting, which are both hallmarks of a memory lymphocyte response.

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Section: Discussioncontrasting

confidence: 58%

Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model

Vissers

Esch²,

Hofman³

et al. 2005

Eur Respir J

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“…In this study, we analyzed the molecular mechanism by which OprI exerts its adjuvant effect and examined whether transmucosal administration of OprI could alter the immunological and physiological manifestations of asthma using a mouse model of OVAinduced allergic asthma (17). We found that OprI affects the function of APCs by enhancing their ability to trigger naive T cells and confer to them the capacity to induce the development of Th1 cells.…”

Section: Asthma Is An Inflammatory Lung Disease That Is Initiated Andmentioning

confidence: 99%

Lipoprotein I, a TLR2/4 Ligand Modulates Th2-Driven Allergic Immune Responses

Revets

Pynaert

Grooten

et al. 2005

The Journal of Immunology

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Asthma is an inflammatory lung disease that is initiated and directed by Th2 and inhibited by Th1 cytokines. Microbial infections have been shown to prevent allergic responses by inducing the secretion of the Th1 cytokines IL-12 and IFN-γ. In this study, we examined whether administration of lipoprotein I (OprI) from Pseudomonas aeruginosa could prevent the inflammatory and physiological manifestations of asthma in a murine model of OVA-induced allergic asthma. OprI triggered dendritic cells to make IL-12 and TNF-α, with subsequent IFN-γ production from T cells. OprI stimulation of dendritic cells involved both TLR2 and TLR4. Intranasal coadministration of OprI with OVA allergen resulted in a significant decrease in airway eosinophilia and Th2 (IL-4 and IL-13) cytokines and this effect was sustained after repeated allergen challenge. The immediate suppressive effect of OprI (within 2 days of administration) was accompanied by an increase in Th1 cytokine IFN-γ production and a significant, but transient infiltration of neutrophils. OprI did not redirect the immune system toward a Th1 response since no increased activation of locally recruited Th1 cells could be observed upon repeated challenge with allergen. Our data show for the first time that a bacterial lipoprotein can modulate allergen-specific Th2 effector cells in an allergic response in vivo for a prolonged period via stimulation of the TLR2/4 signaling pathway.

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“…In addition, they play a role in in vivo Th2 cell priming and a critical role in secondary Th2 responses [14, 15, 39, 194, 195, 196, 197, 198, 199, 200]. In contrast to an apparent role for DC in allergic asthma, the function of macrophages remains unclear despite their obvious abundance within the lungs and inflammatory infiltrates [17, 201, 202, 203, 204, 205, 206]. …”

Section: Lessons From Mouse Models About Pathogenesismentioning

confidence: 99%

Do Mouse Models of Allergic Asthma Mimic Clinical Disease?

Epstein¹

2004

Int Arch Allergy Immunol

132

108

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Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing (1) the factors influencing the pathophysiological responses during the initiation and perpetuation of disease, (2) the utility of mouse models for studying clinical manifestations of disease, and (3) the applicability of mouse models for testing new treatments for allergic asthma.

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Antigen Presentation by Local Macrophages Promotes Nonallergic Airway Responses in Sensitized Mice

Cited by 14 publications

References 34 publications

Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model

Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model

Lipoprotein I, a TLR2/4 Ligand Modulates Th2-Driven Allergic Immune Responses

Do Mouse Models of Allergic Asthma Mimic Clinical Disease?

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