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

Abstract

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.

IL‐10 signaling in dendritic cells is required for tolerance induction in a murine model of allergic airway inflammation

“…S5). Extensive effects of IL‐10 on macrophages have been previously described and allergic airway inflammation in mice has been previously reported to be suppressed/regulated by macrophages . In addition, lung‐resident tissue macrophages have been suggested to promote airway tolerance by generating Treg .…”

The allergic cascade: Review of the most important molecules in the asthmatic lung

“…On the one hand, macrophages are recruited to the airways of allergic subjects following allergen challenge [61]. They secrete cytokines and chemokines, including IL-1, IFN-␥, TNF-␣, IL-6, CCL2, CCL3, and CXCL8 [62,63], what results in the recruitment and activation of other inflammatory cells [64]. IL-6 is involved in macrophage differentiation [65].…”

Allergic Inflammation in Aspergillus fumigatus-Induced Fungal Asthma

“…It was apparent that AMs from unsensitized mice, which are not antigen-primed and have better regenerative capacity, provided protection against asthmatic symptoms [43,44]. Vissers et al [45] further demonstrated that intravenously administered allergen-loaded macrophages accumulate in the spleen and induce indirect, but long-term, allergen-specific immunosuppressive effects through regulatory T cells (Tregs). Similar observations have been made in human asthmatic studies where suppression of T cell proliferation by AMs is thought to be mediated through cell-cell interactions [46].…”