Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein
<b>Background/Objectives</b>: Acute otitis media is a common pediatric infection caused primarily by nontypeable <i>Haemophilus influenzae</i>. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1/PD-L1 pathway ha...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/2076-393X/13/3/313 |
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| author | Kazuhiro Yoshinaga Takashi Hirano Shingo Umemoto Yoshinori Kadowaki Takayuki Matsunaga Masashi Suzuki |
| author_facet | Kazuhiro Yoshinaga Takashi Hirano Shingo Umemoto Yoshinori Kadowaki Takayuki Matsunaga Masashi Suzuki |
| author_sort | Kazuhiro Yoshinaga |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Acute otitis media is a common pediatric infection caused primarily by nontypeable <i>Haemophilus influenzae</i>. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1/PD-L1 pathway has been extensively studied for its role in tumor immunity, its impact on mucosal immunity, particularly in vaccine responses, is unclear. <b>Methods</b>: BALB/c mice were intranasally immunized with nontypeable <i>H. influenzae</i> outer membrane protein and treated with anti-PD-L1 antibodies. Immune responses were evaluated in middle ear mucosa (MEM), the cervical lymph node, and the spleen using an enzyme-linked immunosorbent assay, an enzyme-linked immunospot assay, and flow cytometry. The effects on CD4<sup>+</sup> T cells, T follicular helper (Tfh) cells, and B-cell differentiation were analyzed. <b>Results</b>: Anti-PD-L1 antibody treatment increased CD3<sup>+</sup>CD4<sup>+</sup>CD185<sup>+</sup> (CXCR5<sup>+</sup>) Tfh cells in MEM, which play a crucial role in supporting B-cell activation and antibody production. This correlated with a significant increase in IgA- and IgG-producing cells in MEM, which enhanced local bacterial clearance. Although B-cell activation and differentiation into plasmablasts were observed in MEM, no significant changes were noted in the cervical lymph node and spleen, suggesting a localized enhancement of mucosal immunity. <b>Conclusions</b>: Anti-PD-L1 antibodies promoted Tfh cell expansion and B-cell differentiation in MEM, leading to enhanced antibody production and improved bacterial clearance. These findings suggest that PD-L1 blockade can potentiate mucosal vaccine-induced immunity by strengthening local humoral responses. This supports its potential application in developing intranasal vaccines for acute otitis media. |
| format | Article |
| id | doaj-art-d85b3b65633f4fa9a14f34f187a03938 |
| institution | DOAJ |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-d85b3b65633f4fa9a14f34f187a039382025-08-20T02:43:04ZengMDPI AGVaccines2076-393X2025-03-0113331310.3390/vaccines13030313Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane ProteinKazuhiro Yoshinaga0Takashi Hirano1Shingo Umemoto2Yoshinori Kadowaki3Takayuki Matsunaga4Masashi Suzuki5Department of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Otorhinolaryngology& Head and Neck Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan<b>Background/Objectives</b>: Acute otitis media is a common pediatric infection caused primarily by nontypeable <i>Haemophilus influenzae</i>. With rising antibiotic resistance, vaccines are essential for combating this public health issue. Although the PD-1/PD-L1 pathway has been extensively studied for its role in tumor immunity, its impact on mucosal immunity, particularly in vaccine responses, is unclear. <b>Methods</b>: BALB/c mice were intranasally immunized with nontypeable <i>H. influenzae</i> outer membrane protein and treated with anti-PD-L1 antibodies. Immune responses were evaluated in middle ear mucosa (MEM), the cervical lymph node, and the spleen using an enzyme-linked immunosorbent assay, an enzyme-linked immunospot assay, and flow cytometry. The effects on CD4<sup>+</sup> T cells, T follicular helper (Tfh) cells, and B-cell differentiation were analyzed. <b>Results</b>: Anti-PD-L1 antibody treatment increased CD3<sup>+</sup>CD4<sup>+</sup>CD185<sup>+</sup> (CXCR5<sup>+</sup>) Tfh cells in MEM, which play a crucial role in supporting B-cell activation and antibody production. This correlated with a significant increase in IgA- and IgG-producing cells in MEM, which enhanced local bacterial clearance. Although B-cell activation and differentiation into plasmablasts were observed in MEM, no significant changes were noted in the cervical lymph node and spleen, suggesting a localized enhancement of mucosal immunity. <b>Conclusions</b>: Anti-PD-L1 antibodies promoted Tfh cell expansion and B-cell differentiation in MEM, leading to enhanced antibody production and improved bacterial clearance. These findings suggest that PD-L1 blockade can potentiate mucosal vaccine-induced immunity by strengthening local humoral responses. This supports its potential application in developing intranasal vaccines for acute otitis media.https://www.mdpi.com/2076-393X/13/3/313acute otitis mediaPD-1PD-L1humoral immunityT follicular helper cells |
| spellingShingle | Kazuhiro Yoshinaga Takashi Hirano Shingo Umemoto Yoshinori Kadowaki Takayuki Matsunaga Masashi Suzuki Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein Vaccines acute otitis media PD-1 PD-L1 humoral immunity T follicular helper cells |
| title | Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein |
| title_full | Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein |
| title_fullStr | Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein |
| title_full_unstemmed | Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein |
| title_short | Effect of Anti-Programmed Cell Death-1 Antibody on Middle Ear Mucosal Immune Response to Intranasal Administration of <i>Haemophilus influenzae</i> Outer Membrane Protein |
| title_sort | effect of anti programmed cell death 1 antibody on middle ear mucosal immune response to intranasal administration of i haemophilus influenzae i outer membrane protein |
| topic | acute otitis media PD-1 PD-L1 humoral immunity T follicular helper cells |
| url | https://www.mdpi.com/2076-393X/13/3/313 |
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