GM-CSF Availability Determines LPS-Mediated Functions in Allergic Inflammation

Lipopolysaccharide (LPS) can either promote or prevent T helper-2 (Th2) cell-allergic responses. However, the underlying mechanism remains unknown. We show here that monocytes play an essential role in mediating LPS-induced protection from allergic inflammation. Sensitization of mice with house-dust-mite (HDM) in the presence of low-dose lipopolysaccharide (LPS) triggered activation and cytokine production by monocytic cells, which in turn activated CD11b+migratory dendritic cells (mDC2s) for interleukin-12 (IL-12) production and prevention of Th2 cell development. The ability of monocytes to respond to low-dose LPS depended upon GM-CSF priming, and so inert allergens such as OVA, that did not elicit GM-CSF production, failed to activate monocytes after OVA + low-dose LPS sensitization. Consequently, Th2 cell responses normally developed even in the presence of LPS. Thus, the availability of GM-CSF dictates the ability of LPS to either promote or suppress allergic-Th2 cell responses. This knowledge may offer new strategies to control allergic airway disease.