Pertactin contributes to shedding and transmission of Bordetella bronchiseptica

Autor: Kalyan K. Dewan, Amanda D. Caulfield, Uriel Blas-Machado, Longhuan Ma, Shannon M. Wagner, Israel Rivera, Eric T. Harvill, Yang Su, Dawn L. Taylor-Mulneix, Bodo Linz
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Bacterial Diseases
Bordetella pertussis
Bordetella
Physiology
Respiratory System
Pathology and Laboratory Medicine
Bacterial Adhesion
White Blood Cells
Mice
Medical Conditions
Animal Cells
Immune Physiology
Medicine and Health Sciences
Virulence Factors
Bordetella
Biology (General)
Immune Response
Bacterial Shedding
Mice
Inbred C3H
Bordetella bronchiseptica
biology
Bacterial Pathogens
Body Fluids
Infectious Diseases
medicine.anatomical_structure
Medical Microbiology
Female
Anatomy
Nasal Cavity
Pathogens
Cellular Types
Pertactin
Research Article
Bacterial Outer Membrane Proteins
QH301-705.5
Immune Cells
Immunology
Context (language use)
Microbiology
Signs and Symptoms
Immune system
Pertussis
Virology
Genetics
medicine
Animals
Humans
Microbial Pathogens
Molecular Biology
Secretion
Bordetella Infections
Inflammation
Blood Cells
Bacteria
Macrophages
Organisms
Biology and Life Sciences
Cell Biology
RC581-607
biology.organism_classification
Mucus
respiratory tract diseases
Mice
Inbred C57BL
Alveolar Epithelial Cells
Parasitology
Clinical Medicine
Immunologic diseases. Allergy
Bordetella Pertussis
Physiological Processes
Spleen
Respiratory tract
Zdroj: PLoS Pathogens, Vol 17, Iss 8, p e1009735 (2021)
PLoS Pathogens, Vol 17, Iss 8 (2021)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Whooping cough is resurging in the United States despite high vaccine coverage. The rapid rise of Bordetella pertussis isolates lacking pertactin (PRN), a key vaccine antigen, has led to concerns about vaccine-driven evolution. Previous studies showed that pertactin can mediate binding to mammalian cells in vitro and act as an immunomodulatory factor in resisting neutrophil-mediated clearance. To further investigate the role of PRN in vivo, we examined the functions of pertactin in the context of a more naturally low dose inoculation experimental system using C3H/HeJ mice that is more sensitive to effects on colonization, growth and spread within the respiratory tract, as well as an experimental approach to measure shedding and transmission between hosts. A B. bronchiseptica pertactin deletion mutant was found to behave similarly to its wild-type (WT) parental strain in colonization of the nasal cavity, trachea, and lungs of mice. However, the pertactin-deficient strain was shed from the nares of mice in much lower numbers, resulting in a significantly lower rate of transmission between hosts. Histological examination of respiratory epithelia revealed that pertactin-deficient bacteria induced substantially less inflammation and mucus accumulation than the WT strain and in vitro assays verified the effect of PRN on the induction of TNF-α by murine macrophages. Interestingly, only WT B. bronchiseptica could be recovered from the spleen of infected mice and were further observed to be intracellular among isolated splenocytes, indicating that pertactin contributes to systemic dissemination involving intracellular survival. These results suggest that pertactin can mediate interactions with immune cells and augments inflammation that contributes to bacterial shedding and transmission between hosts. Understanding the relative contributions of various factors to inflammation, mucus production, shedding and transmission will guide novel strategies to interfere with the reemergence of pertussis.
Author summary B. pertussis strains lacking pertactin have been rising in prevalence especially in countries using acellular vaccines containing pertactin as a key, membrane-associated surface antigen. Previous in vivo studies revealed immunomodulatory properties of pertactin in conventional B. pertussis infection models in which roughly one million bacteria are delivered into lungs, leading to severe pneumonic disease and a strong immune response. However, natural infections begin in the nasopharyngeal region, progress slowly during a prolonged catarrhal stage, only later reaching the trachea and rarely involve the lungs. In this study, a more natural experimental system takes advantage of the ability of B. bronchiseptica, a closely related species, to naturally colonize mice with inocula as low as 5 colony forming units (CFU). In this system B. bronchiseptica can be observed to efficiently colonize, grow, spread within the respiratory tract, is shed from the nares, and transmits between hosts, allowing each of these steps to be measured and studied. Under these conditions, an isogenic pertactin deletion strain was indistinguishable from its parental strain in its abilities to colonize, grow in numbers and spread within the respiratory tract. However, the pertactin-deficient mutant was shed from these mice in lower numbers than wild type, and was defective in transmission between mice. These assays reveal novel roles of pertactin in the induction of inflammation, mucus production, shedding and transmission.
Databáze: OpenAIRE
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