Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
Denis Bedoret, … , Pierre Lekeux, Fabrice Bureau
Denis Bedoret, … , Pierre Lekeux, Fabrice Bureau
Published November 9, 2009
Citation Information: J Clin Invest. 2009;119(12):3723-3738. https://doi.org/10.1172/JCI39717.
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Research Article Pulmonology

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

Abstract

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC–driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LPS develop allergic asthma. What prevents most people from mounting a lung DC–driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10–dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions.

Authors

Denis Bedoret, Hugues Wallemacq, Thomas Marichal, Christophe Desmet, Florence Quesada Calvo, Emmanuelle Henry, Rodrigue Closset, Benjamin Dewals, Caroline Thielen, Pascal Gustin, Laurence de Leval, Nico Van Rooijen, Alain Le Moine, Alain Vanderplasschen, Didier Cataldo, Pierre-Vincent Drion, Muriel Moser, Pierre Lekeux, Fabrice Bureau

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Figure 2

IMs are able to suppress the induction of airway allergy by OVA-pulsed, LPS-stimulated DCs.

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IMs are able to suppress the induction of airway allergy by OVA-pulsed, ...
(A–G) Naive BALB/c mice were injected i.t. with PBS-BMDCs, OVALPS-BMDCs, OVALPS-BMDCs/AMs, OVALPS-BMDCs/IMs, OVALPS-BMDCsIMmemb, or OVALPS-BMDCs/IMs/AMs. From day 10 to day 14, mice were exposed to OVA aerosols. Twenty-four hours after the last challenge, the severity of airway allergy was evaluated. (A) BALF was subjected to total and differential cell counts. (B and C) Lung sections were stained with either H&E (B) or PAS (C) (original magnification, ×100). (D) Levels of OVA-specific IgE were measured in serum samples by ELISA. OVA-specific IgE levels are expressed as AU. (E and F) MLN cells were restimulated in vitro for 3 days with 50 μg/ml OVA. (E) The proliferation was measured as [3H]thymidine incorporation during the last 16 hours. (F) Culture supernatants were assayed for IL-4, IFN-γ, IL-5, and IL-13 by ELISA. (G) AHR to various doses of methacholine was assessed by invasive measurement of dynamic resistance. *P < 0.05 versus OVALPS-BMDCs and OVALPS-BMDCs/AMs (A and D–G).