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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...

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Autores principales: Sedney, Colleen J., Caulfield, Amanda, Dewan, Kaylan K., Blas-Machado, Uriel, Callender, Maiya, Manley, Nancy R., Harvill, Eric T.
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
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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.
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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
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