Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice

Fabrice B., et al.2009. The Journal of Clinical Investigation. 119, 3723-3738

Student: Tsan-Tzu Yang (楊璨滋)                                  Time: 13:10-14:00, May 05, 2010

Commentator: Dr. Chun-Keung Yu (余俊強 博士)             Place: Room 601

Abstract

The respiratory tract is exposed to a lot of microbes in the environment. The component of microbe, such as lipopolysaccharide (LPS), activates dendritic cells (DCs) via CD14, MD2 and toll-like receptor 4 to induce DC-driven Th2 cell responses in allergic asthma (1, 2). Most people have tolerance to LPS-induced allergy; however, the mechanism which prevent most people from LPS-induced Th2 cell responses is unknown. Here, the author identified a group of F4/80⁺CD11c^- cells, namely lung interstitial macrophages (IMs) which have abilities of phagocytosis and stimulating T cell proliferation. For allergic model, mice treated with the bone marrow-derived DCs (BMDCs) stimulated with OVA_LPS plus with or without alveolar macrophages or IMs were then challenged with OVA aerosols. Results showed that mice with OVA_LPS-BMDCs developed bronchoalveolar lavages fluid (BALF) and peribronchial lung tissue eosinophilia and lymphocytosis, accompanied by goblet cell hyperplasia and increased mucus production. Serum levels of OVA-specific IgE, Th2 cytokine production and T cell proliferation in mediastinal lymph nodes (MLNs) were substantially decreased in mice treated with OVA_LPS-BMDCs/IMs. OVA_LPS-BMDCs/IMs inhibited primary T cell proliferation and IL-4 production. For in vitro model, the lung DCs isolated from BALB/c mice were stimulated with OVA_LPS in the presence or absence of AMs or IMs. OVA_LPS-induced DCs migration, CD80 and MHC II expression, and IL-12 secretion were significantly decreased when OVA_LPS-stimlated DCs were co-cultured with IMs. Notably, IMs produced more IL-10 spontaeneously or after stimulated by OVA_LPS. However, IL-10^-/- IMs reduced ability to inhibit OVA_LPS-induced lung DCs migration and maturation, BALF eosinophilia and lymphocytosis, and IL-4 expression of MLN cells. Depleting IMs using anti-F4/80 demonstrated that IMs prevented LPS-induced Th2 responses to inhaled antigen. Taken together, IMs are important for inhibit DC maturation and migration through IL-10 production and for preventing Th2 cell responses in allergic asthma in the mice challenged with LPS.

References

1. Douwes, J., et al. 2000. beta-D-glucan and endotoxin in house dust and peak flow variability in children. Am. J. Respir. Crit. Care Med. 162:1348-1354.

2. Hammad, H., et al. 2009. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat. Med. 15:410-416.