Particularly, allergens, such as house dust mites (HDM), are often contaminated with lipopolysaccharide/endotoxin (LPS), and the contribution of LPS to allergenicity has long been of interest and a topic of many reviews ( Eder and von Mutius, 2004 Liu and Leung, 2006 Radon, 2006). The initial priming (or “sensitization”) of allergen-specific CD4 + T cells is influenced by the interplay between exposures to aeroallergens and their natural content in microbial products ( Bachus et al., 2019 Eder et al., 2004, 2005 Eisenbarth et al., 2002 Hammad et al., 2009 Vercelli, 2008 Wilson et al., 2012). Its leading cause is the aberrant activation of allergen-specific T helper 2 (Th2) cells ( Ballesteros-Tato et al., 2016 Leomicronn, 2017 Leon and Ballesteros-Tato, 2021). Thus, GM-CSF produced by non-classical monocytes acts as a rheostat that fine-tunes the pathogenic and therapeutic functions of LPS.Īllergic airway disease is the most common chronic disorder worldwide ( Dharmage et al., 2019).
Treatment with GM-CSF, however, restores the protective effects of LPS. Hence, the therapeutic effect of LPS is restricted to allergens with this enzymatic activity. Importantly, only allergens with cysteine protease activity trigger GM-CSF production by non-classical monocytes. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate monocyte-derived DCs from classical Ly6C hi monocytes that instruct mDC2s for Th2 cell suppression. In the absence of GM-CSF, LPS can favor pathogenic Th2 cell responses by supporting the trafficking of lung-migratory dendritic cells (mDC2s) into the lung-draining lymph node. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by non-classical monocytes. However, the underlying mechanism remains unknown. Lipopolysaccharide (LPS) can either promote or prevent T helper 2 (Th2) cell allergic responses.
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