Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli
IntroductionOrofacial Granulomatosis (OFG) is a rare chronic inflammatory disorder characterized by persistent or recurrent swelling of the lips and oral mucosa, often accompanied by granulomatous inflammation in the orofacial region with limited effective treatment options available. Emerging evide...
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Frontiers Media S.A.
2025-05-01
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| author | Francesco Palestra Luca Modestino Annagioia Ventrici Arianna Monteforte Gina Memoli Anne Lise Ferrara Leonardo Cristinziano Remo Poto Francesca Wanda Rossi Francesca Wanda Rossi Francesca Wanda Rossi Gilda Varricchi Gilda Varricchi Gilda Varricchi Gilda Varricchi Amato De Paulis Amato De Paulis Amato De Paulis Gianni Marone Gianni Marone Gianni Marone Giuseppe Spadaro Giuseppe Spadaro Giuseppe Spadaro Angelica Petraroli Stefania Loffredo Stefania Loffredo Stefania Loffredo Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero |
| author_facet | Francesco Palestra Luca Modestino Annagioia Ventrici Arianna Monteforte Gina Memoli Anne Lise Ferrara Leonardo Cristinziano Remo Poto Francesca Wanda Rossi Francesca Wanda Rossi Francesca Wanda Rossi Gilda Varricchi Gilda Varricchi Gilda Varricchi Gilda Varricchi Amato De Paulis Amato De Paulis Amato De Paulis Gianni Marone Gianni Marone Gianni Marone Giuseppe Spadaro Giuseppe Spadaro Giuseppe Spadaro Angelica Petraroli Stefania Loffredo Stefania Loffredo Stefania Loffredo Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero |
| author_sort | Francesco Palestra |
| collection | DOAJ |
| description | IntroductionOrofacial Granulomatosis (OFG) is a rare chronic inflammatory disorder characterized by persistent or recurrent swelling of the lips and oral mucosa, often accompanied by granulomatous inflammation in the orofacial region with limited effective treatment options available. Emerging evidence suggests an immune dysregulation in the development and progression of OFG. Immune cells, including monocytes and neutrophils (PMNs), are involved in autoimmune and inflammatory diseases by releasing pro-inflammatory and immunomodulatory molecules.MethodsConsidering that microbial agents have been suggested as potential triggers for OFG, in this study we evaluated the effect of LPS, fMLP and PMA on the activation of monocytes and PMNs purified by 11 OFG patients and 11 sex-and age-matched healthy donors (HDs).ResultsUpon stimulation, OFG-derived monocytes displayed a higher release of pro-inflammatory cytokines (CXCL8/IL-8, IL-6, TNF-α, IL-33) compared to HDs. Conversely, OFG-derived monocytes showed a lower release of IL-10, IFN-γ compared to HDs. Upon stimulation, peripheral PMNs from OFG patients released large amounts of TNF-α and MPO compared to HDs. In addition, OFG-derived PMNs showed high percentages of activated PMNs (CD62L-) and increased ROS production compared to HDs. Compared to HDs, OFG patients presented higher serum levels of MMP-9, MPO and TNF-α, together with MPO-DNA complexes and citrullinated histone H3 (CitH3) (two biomarkers for neutrophil extracellular traps).DiscussionThese preliminary data suggest that in presence of various stimuli, monocytes and PMNs of OFG patients displayed an activated phenotype compared to HDs. Unraveling the interplay between bacterial triggers and immune cell function in OFG will be necessary to elucidate mechanisms driving this complex disease and identify novel therapeutic targets for improved management of OFG patients. |
| format | Article |
| id | doaj-art-49ec71d64ece45efae18b0d182f5b812 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-49ec71d64ece45efae18b0d182f5b8122025-08-20T02:14:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15224951522495Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuliFrancesco Palestra0Luca Modestino1Annagioia Ventrici2Arianna Monteforte3Gina Memoli4Anne Lise Ferrara5Leonardo Cristinziano6Remo Poto7Francesca Wanda Rossi8Francesca Wanda Rossi9Francesca Wanda Rossi10Gilda Varricchi11Gilda Varricchi12Gilda Varricchi13Gilda Varricchi14Amato De Paulis15Amato De Paulis16Amato De Paulis17Gianni Marone18Gianni Marone19Gianni Marone20Giuseppe Spadaro21Giuseppe Spadaro22Giuseppe Spadaro23Angelica Petraroli24Stefania Loffredo25Stefania Loffredo26Stefania Loffredo27Maria Rosaria Galdiero28Maria Rosaria Galdiero29Maria Rosaria Galdiero30Department of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, National Research Council (CNR), Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, National Research Council (CNR), Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyInstitute of Experimental Endocrinology and Oncology, National Research Council (CNR), Naples, ItalyDepartment of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyDepartment of Internal Medicine and Clinical Immunology, University Hospital of Naples Federico II, Naples, ItalyCenter for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, ItalyIntroductionOrofacial Granulomatosis (OFG) is a rare chronic inflammatory disorder characterized by persistent or recurrent swelling of the lips and oral mucosa, often accompanied by granulomatous inflammation in the orofacial region with limited effective treatment options available. Emerging evidence suggests an immune dysregulation in the development and progression of OFG. Immune cells, including monocytes and neutrophils (PMNs), are involved in autoimmune and inflammatory diseases by releasing pro-inflammatory and immunomodulatory molecules.MethodsConsidering that microbial agents have been suggested as potential triggers for OFG, in this study we evaluated the effect of LPS, fMLP and PMA on the activation of monocytes and PMNs purified by 11 OFG patients and 11 sex-and age-matched healthy donors (HDs).ResultsUpon stimulation, OFG-derived monocytes displayed a higher release of pro-inflammatory cytokines (CXCL8/IL-8, IL-6, TNF-α, IL-33) compared to HDs. Conversely, OFG-derived monocytes showed a lower release of IL-10, IFN-γ compared to HDs. Upon stimulation, peripheral PMNs from OFG patients released large amounts of TNF-α and MPO compared to HDs. In addition, OFG-derived PMNs showed high percentages of activated PMNs (CD62L-) and increased ROS production compared to HDs. Compared to HDs, OFG patients presented higher serum levels of MMP-9, MPO and TNF-α, together with MPO-DNA complexes and citrullinated histone H3 (CitH3) (two biomarkers for neutrophil extracellular traps).DiscussionThese preliminary data suggest that in presence of various stimuli, monocytes and PMNs of OFG patients displayed an activated phenotype compared to HDs. Unraveling the interplay between bacterial triggers and immune cell function in OFG will be necessary to elucidate mechanisms driving this complex disease and identify novel therapeutic targets for improved management of OFG patients.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1522495/fullcytokines/chemokinesROSNETsbacterial stimuliinflammationimmunopathogenesis |
| spellingShingle | Francesco Palestra Luca Modestino Annagioia Ventrici Arianna Monteforte Gina Memoli Anne Lise Ferrara Leonardo Cristinziano Remo Poto Francesca Wanda Rossi Francesca Wanda Rossi Francesca Wanda Rossi Gilda Varricchi Gilda Varricchi Gilda Varricchi Gilda Varricchi Amato De Paulis Amato De Paulis Amato De Paulis Gianni Marone Gianni Marone Gianni Marone Giuseppe Spadaro Giuseppe Spadaro Giuseppe Spadaro Angelica Petraroli Stefania Loffredo Stefania Loffredo Stefania Loffredo Maria Rosaria Galdiero Maria Rosaria Galdiero Maria Rosaria Galdiero Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli Frontiers in Immunology cytokines/chemokines ROS NETs bacterial stimuli inflammation immunopathogenesis |
| title | Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli |
| title_full | Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli |
| title_fullStr | Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli |
| title_full_unstemmed | Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli |
| title_short | Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli |
| title_sort | differential activation of monocytes and pmns in orofacial granulomatosis patients induced by bacterial and non bacterial stimuli |
| topic | cytokines/chemokines ROS NETs bacterial stimuli inflammation immunopathogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1522495/full |
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