Molecular Mechanisms by which Bacterial Lipopolysaccharides Prevent or Promote the Development of Asthma and Allergic Diseases in Humans Revealed
Lipopolysaccharide (LPS) can promote or prevent allergic reactions of T helper cells (Th2), but the molecular mechanism behind it is not clear to researchers at present; immunologists have long been confused about LPS, which is a lipopolysaccharide molecule of bacteria, which can help form the cell wall of gram-negative bacteria; many experiments have shown that LPS exposure may protect the body against asthma or allergic diseases during exposure to environmental allergens; however, other studies have suggested that the presence of LPS during exposure to environmental allergens may have the opposite effect, which can promote the occurrence of asthma and other allergic diseases.
Recently, in a study published in Cell Reports entitled 'GM-CSF production by non-classical monocytes antagonistic controls LPS-driven functions in allergic inflammation,' scientists from the University of Alabama and other institutions found through the study that the key to LPS promoting or preventing the body's anaphylaxis lies in the allergen itself.
Further understanding of the sensitization mechanisms of allergic diseases may provide novel strategies to control allergic airway diseases, especially asthma; the global epidemic of asthma, including the dramatic increase in prevalence in developed countries since the 1960s, affects the health of approximately 300 million children and adults worldwide. In the study, researchers Leon and colleagues unveiled the antagonistic mechanism by which LPS promotes or prevents allergic diseases by activating or inhibiting Th2 immune cells, and the findings also identified the special role of immune cells called classical monocytes and non-classical monocytes.
First, the presence of cysteine protease activity in airborne allergens is required for bacterial LPS to exert its protective effect, while allergens containing cysteine protease activity (such as house dust mites or papain) may lead to the preventive effect of the body on sensitization in the presence of LPS; conversely, the German cockroach principle of airborne allergy lacking cysteine protease activity will still promote the occurrence of sensitization in the presence of LPS.
Cysteine proteases can induce non-classical monocytes in the lungs to produce the cytokine GM-CSF (granulocyte-macrophage colony-stimulating factor) through a mechanism that is not clear, and GM-CSF signaling can control LPS to inhibit Th2 cell responses to allergens, such as house dust mites. Therefore, because the protective effect of LPS depends on GM-CSF, the beneficial effect of LPS is often limited to allergens with cysteine protease activity, said researcher Leno.
In the presence of GM-CSF, LPS can initiate an immune response by supporting the transport of pulmonary migratory dendritic cells to the draining lymph nodes of the lung and facilitate a pathogenic Th2 cell response; however, when non-classical monocytes produce GM-CSF, LPS and GM-CSF can synergistically differentiate classical monocytes into monocyte-derived dendritic cells, thereby directing pulmonary migratory dendritic cells to inhibit allergic airway inflammation of Th2 cells by producing interleukin-12. The results of this study suggest that GM-CSF separates opposing functions of LPS in eliciting allergen-specific Th2 cell responses, and therefore, affected by genetic diversity or environmental factors, host differential sensitivity to GM-CSF and/or LPS may significantly affect the risk of allergic sensitization, and understanding these interactions may help develop novel therapeutic measures to circumvent or even reverse allergic diseases.
The present study involves the investigation of different allergen sensitization in mouse models, transcriptional profiling, and in vivo loss-of-function and gain-of-function assays. Taken together, those findings suggest that GM-CSF produced by non-classical monocytes may be capable of acting as a rheostat to fine-tune the pathogenic properties and therapeutic functions of LPS.
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