Cargando…
Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
The increased susceptibility of neonates to specific pathogens has previously been attributed to an underdeveloped immune system. More recent data suggest neonates have effective protection against most pathogens but are particularly susceptible to those that target immune functions specific to neon...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968397/ https://www.ncbi.nlm.nih.gov/pubmed/36855631 http://dx.doi.org/10.3389/fimmu.2023.1125794 |
_version_ | 1784897497395625984 |
---|---|
author | Sedney, Colleen J. Caulfield, Amanda Dewan, Kaylan K. Blas-Machado, Uriel Callender, Maiya Manley, Nancy R. Harvill, Eric T. |
author_facet | Sedney, Colleen J. Caulfield, Amanda Dewan, Kaylan K. Blas-Machado, Uriel Callender, Maiya Manley, Nancy R. Harvill, Eric T. |
author_sort | Sedney, Colleen J. |
collection | PubMed |
description | The increased susceptibility of neonates to specific pathogens has previously been attributed to an underdeveloped immune system. More recent data suggest neonates have effective protection against most pathogens but are particularly susceptible to those that target immune functions specific to neonates. Bordetella pertussis (Bp), the causative agent of “whooping cough”, causes more serious disease in infants attributed to its production of pertussis toxin (PTx), although the neonate-specific immune functions it targets remain unknown. Problematically, the rapid development of adult immunity in mice has confounded our ability to study interactions of the neonatal immune system and its components, such as virtual memory T cells which are prominent prior to the maturation of the thymus. Here, we examine the rapid change in susceptibility of young mice and define a period from five- to eight-days-old during which mice are much more susceptible to Bp than mice even a couple days older. These more narrowly defined “neonatal” mice display significantly increased susceptibility to wild type Bp but very rapidly and effectively respond to and control Bp lacking PTx, more rapidly even than adult mice. Thus, PTx efficiently blocks some very effective form(s) of neonatal protective immunity, potentially providing a tool to better understand the neonatal immune system. The rapid clearance of the PTx mutant correlates with the early accumulation of neutrophils and T cells and suggests a role for PTx in disrupting their accumulation. These results demonstrate a striking age-dependent response to Bp, define an early age of extreme susceptibility to Bp, and demonstrate that the neonatal response can be more efficient than the adult response in eliminating bacteria from the lungs, but these neonatal functions are substantially blocked by PTx. This refined definition of “neonatal” mice may be useful in the study of other pathogens that primarily infect neonates, and PTx may prove a particularly valuable tool for probing the poorly understood neonatal immune system. |
format | Online Article Text |
id | pubmed-9968397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99683972023-02-27 Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis Sedney, Colleen J. Caulfield, Amanda Dewan, Kaylan K. Blas-Machado, Uriel Callender, Maiya Manley, Nancy R. Harvill, Eric T. Front Immunol Immunology The increased susceptibility of neonates to specific pathogens has previously been attributed to an underdeveloped immune system. More recent data suggest neonates have effective protection against most pathogens but are particularly susceptible to those that target immune functions specific to neonates. Bordetella pertussis (Bp), the causative agent of “whooping cough”, causes more serious disease in infants attributed to its production of pertussis toxin (PTx), although the neonate-specific immune functions it targets remain unknown. Problematically, the rapid development of adult immunity in mice has confounded our ability to study interactions of the neonatal immune system and its components, such as virtual memory T cells which are prominent prior to the maturation of the thymus. Here, we examine the rapid change in susceptibility of young mice and define a period from five- to eight-days-old during which mice are much more susceptible to Bp than mice even a couple days older. These more narrowly defined “neonatal” mice display significantly increased susceptibility to wild type Bp but very rapidly and effectively respond to and control Bp lacking PTx, more rapidly even than adult mice. Thus, PTx efficiently blocks some very effective form(s) of neonatal protective immunity, potentially providing a tool to better understand the neonatal immune system. The rapid clearance of the PTx mutant correlates with the early accumulation of neutrophils and T cells and suggests a role for PTx in disrupting their accumulation. These results demonstrate a striking age-dependent response to Bp, define an early age of extreme susceptibility to Bp, and demonstrate that the neonatal response can be more efficient than the adult response in eliminating bacteria from the lungs, but these neonatal functions are substantially blocked by PTx. This refined definition of “neonatal” mice may be useful in the study of other pathogens that primarily infect neonates, and PTx may prove a particularly valuable tool for probing the poorly understood neonatal immune system. Frontiers Media S.A. 2023-02-08 /pmc/articles/PMC9968397/ /pubmed/36855631 http://dx.doi.org/10.3389/fimmu.2023.1125794 Text en Copyright © 2023 Sedney, Caulfield, Dewan, Blas-Machado, Callender, Manley and Harvill https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Sedney, Colleen J. Caulfield, Amanda Dewan, Kaylan K. Blas-Machado, Uriel Callender, Maiya Manley, Nancy R. Harvill, Eric T. Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis |
title | Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
|
title_full | Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
|
title_fullStr | Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
|
title_full_unstemmed | Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
|
title_short | Novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to Bordetella pertussis
|
title_sort | novel murine model reveals an early role for pertussis toxin in disrupting neonatal immunity to bordetella pertussis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968397/ https://www.ncbi.nlm.nih.gov/pubmed/36855631 http://dx.doi.org/10.3389/fimmu.2023.1125794 |
work_keys_str_mv | AT sedneycolleenj novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis AT caulfieldamanda novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis AT dewankaylank novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis AT blasmachadouriel novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis AT callendermaiya novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis AT manleynancyr novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis AT harvillerict novelmurinemodelrevealsanearlyroleforpertussistoxinindisruptingneonatalimmunitytobordetellapertussis |