Opposing effects of acellular and whole cell pertussis vaccines on<i>Bordetella pertussis</i>biofilm formation, Siglec-F+ neutrophil recruitment and bacterial clearance in mouse nasal tissues
Abstract Despite global vaccination, pertussis caused byBordetella pertussis(Bp) is resurging. Pertussis resurgence is correlated with the switch from whole cell vaccines (wPV) that elicit TH1/TH17 polarized immune responses to acellular pertussis vaccines (aPV) that elicit primarily TH2 polarized immune responses. One explanation for the increased incidence in aPV-immunized individuals is the lack of bacterial clearance from the nose. To understand the host and bacterial mechanisms that contribute toBppersistence, we evaluated bacterial localization and the immune response in the nasal associated tissues (NT) of naïve and immunized mice followingBpchallenge.Bpresided in the NT of unimmunized and aPV-immunized mice as biofilms. In contrast,Bpbiofilms were not observed in wPV-immunized mice. Following infection, Siglec-F+ neutrophils, critical for eliminatingBpfrom the nose, were recruited to the nose at higher levels in wPV immunized mice compared to aPV immunized mice. Consistent with this observation, the neutrophil chemokine CXCL1 was only detected in the NT of wPV immunized mice. Importantly, the bacteria and immune cells were primarily localized within the NT and were not recovered by nasal lavage (NL). Together, our data suggest that the TH2 polarized immune response generated by aPV vaccination facilitates persistence in the NT by impeding the infiltration of immune effectors and the eradication of biofilms In contrast, the TH1/TH17 immune phenotype generated by wPV, recruits Siglec-F+ neutrophils that rapidly eliminate the bacterial burden and prevent biofilm establishment. Thus, our work shows that aPV and wPV have opposing effects onBpbiofilm formation in the respiratory tract and provides a mechanistic explanation for the inability of aPV vaccination to control bacterial numbers in the nose and prevent transmission.<jats:sec id="s21">Author Summary Acellular pertussis vaccine (aPV) immunized individuals maintain a nasal reservoir ofBordetella pertussis(Bp) and thus have the potential to transmit the infection to vulnerable individuals. Here we provide a mechanistic explanation for the inability of aPV to eliminateBpfrom the nasal cavity. We show that following bacterial challenge of aPV immunized mice, Siglec-F+ neutrophils and other immune effectors are not recruited to the nose. Consequently,Bpremain in the nose and form biofilms. In contrast, whole cell pertussis (wPV) immunized mice produce immune effectors following bacterial challenge that recruit Siglec-F+ neutrophils to the nose.Bpburden is cleared from the nasal tissues, thereby preventing bacterial persistence and the formation of biofilms..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 29. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hall, Jesse M. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.01.23.576795 |
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| PPN (Katalog-ID): |
XBI042287227 |
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| 100 | 1 | |a Hall, Jesse M. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Opposing effects of acellular and whole cell pertussis vaccines on<i>Bordetella pertussis</i>biofilm formation, Siglec-F+ neutrophil recruitment and bacterial clearance in mouse nasal tissues |
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| 520 | |a Abstract Despite global vaccination, pertussis caused byBordetella pertussis(Bp) is resurging. Pertussis resurgence is correlated with the switch from whole cell vaccines (wPV) that elicit TH1/TH17 polarized immune responses to acellular pertussis vaccines (aPV) that elicit primarily TH2 polarized immune responses. One explanation for the increased incidence in aPV-immunized individuals is the lack of bacterial clearance from the nose. To understand the host and bacterial mechanisms that contribute toBppersistence, we evaluated bacterial localization and the immune response in the nasal associated tissues (NT) of naïve and immunized mice followingBpchallenge.Bpresided in the NT of unimmunized and aPV-immunized mice as biofilms. In contrast,Bpbiofilms were not observed in wPV-immunized mice. Following infection, Siglec-F+ neutrophils, critical for eliminatingBpfrom the nose, were recruited to the nose at higher levels in wPV immunized mice compared to aPV immunized mice. Consistent with this observation, the neutrophil chemokine CXCL1 was only detected in the NT of wPV immunized mice. Importantly, the bacteria and immune cells were primarily localized within the NT and were not recovered by nasal lavage (NL). Together, our data suggest that the TH2 polarized immune response generated by aPV vaccination facilitates persistence in the NT by impeding the infiltration of immune effectors and the eradication of biofilms In contrast, the TH1/TH17 immune phenotype generated by wPV, recruits Siglec-F+ neutrophils that rapidly eliminate the bacterial burden and prevent biofilm establishment. Thus, our work shows that aPV and wPV have opposing effects onBpbiofilm formation in the respiratory tract and provides a mechanistic explanation for the inability of aPV vaccination to control bacterial numbers in the nose and prevent transmission.<jats:sec id="s21">Author Summary Acellular pertussis vaccine (aPV) immunized individuals maintain a nasal reservoir ofBordetella pertussis(Bp) and thus have the potential to transmit the infection to vulnerable individuals. Here we provide a mechanistic explanation for the inability of aPV to eliminateBpfrom the nasal cavity. We show that following bacterial challenge of aPV immunized mice, Siglec-F+ neutrophils and other immune effectors are not recruited to the nose. Consequently,Bpremain in the nose and form biofilms. In contrast, whole cell pertussis (wPV) immunized mice produce immune effectors following bacterial challenge that recruit Siglec-F+ neutrophils to the nose.Bpburden is cleared from the nasal tissues, thereby preventing bacterial persistence and the formation of biofilms. | ||
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| 700 | 1 | |a Gupta, Yash A. |4 aut | |
| 700 | 1 | |a Deora, Rajendar |4 aut | |
| 700 | 1 | |a Dubey, Purnima |0 (orcid)0000-0002-5454-8421 |4 aut | |
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