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The nasal cavity displays immune tolerance to commensal bacteria under homeostatic conditions, which is rapidly converted to a pro-inflammatory response upon infection. Yet, the factors that control this conversion are still largely unknown. Here, we provide evidence that Fc gamma receptor III (FcγRIII) stimulation breaks immune tolerance to bacteria in the human nasal cavity through activation of nasal epithelial cells, which are the first line of defense against invading microbes. While under steady-state conditions human nasal epithelial cells were completely non-responsive to Gram-negative bacteria P. aeruginosaor TLR4 ligand LPS, IgG opsonization of bacteria, as occurs upon infection, strongly induced production of pro-inflammatory agents such as IL-6 and IL-8. This breaking of tolerance to bacteria was completely dependent on FcγRIII, which amplified cytokine gene transcription through cross-talk with TLR4. In addition, we identified that epithelial cells from patients suffering from chronic rhinosinusitis with nasal polyps do not display LPS tolerance, thereby providing an explanation for the disturbed host defense responses of these patients. Taken together, these data are the first to identify FcγR expression on nasal epithelial cells, as well as to identify its important role in controlling the balance between tolerance and inflammation in the nasal cavity.

The nasal cavity displays immune tolerance to commensal bacteria under homeostatic conditions, which is rapidly converted to a pro-inflammatory response upon infection. Yet, the factors that control this conversion are still largely unknown. Here, we provide evidence that Fc gamma receptor III (FcγRIII) stimulation breaks immune tolerance to bacteria in the human nasal cavity through activation of nasal epithelial cells, which are the first line of defense against invading microbes. While under steady-state conditions human nasal epithelial cells were completely non-responsive to Gram-negative bacteria P. aeruginosaor TLR4 ligand LPS, IgG opsonization of bacteria, as occurs upon infection, strongly induced production of pro-inflammatory agents such as IL-6 and IL-8. This breaking of tolerance to bacteria was completely dependent on FcγRIII, which amplified cytokine gene transcription through cross-talk with TLR4. In addition, we identified that epithelial cells from patients suffering from chronic rhinosinusitis with nasal polyps do not display LPS tolerance, thereby providing an explanation for the disturbed host defense responses of these patients. Taken together, these data are the first to identify FcγR expression on nasal epithelial cells, as well as to identify its important role in controlling the balance between tolerance and inflammation in the nasal cavity.