Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Bovine neutrophils release extracellular traps and cooperate with macrophages in Mycobacterium avium subsp. paratuberculosis clearance in vitro

I Ladero-Auñon, E Molina, A Holder, J Kolakowski, H Harris, A Urkitza, J Anguita, D Werling, N Elguezabal
doi: https://doi.org/10.1101/2020.12.30.424791
I Ladero-Auñon
1Animal Health Department, Basque Institute for Agricultural Research and Development, NEIKER- Basque Research and Technology Alliance (BRTA), (Derio) Bizkaia, Spain
2Food Quality and Safety Department, University of the Basque Country (UPV/EHU)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Molina
1Animal Health Department, Basque Institute for Agricultural Research and Development, NEIKER- Basque Research and Technology Alliance (BRTA), (Derio) Bizkaia, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A Holder
3Molecular Immunology Laboratory, Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, Hertfordshire, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Kolakowski
3Molecular Immunology Laboratory, Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, Hertfordshire, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H Harris
2Food Quality and Safety Department, University of the Basque Country (UPV/EHU)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A Urkitza
4Bovine Practitioner, Gernika, Bizkaia, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Anguita
5Inflammation and Macrophage Plasticity Laboratory, CIC bioGUNE-Basque Research and Technology Alliance (BRTA), (Derio) Bizkaia, Spain
6Ikerbasque, Basque Foundation for Science, Bilbao, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D Werling
3Molecular Immunology Laboratory, Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, Hertfordshire, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
N Elguezabal
1Animal Health Department, Basque Institute for Agricultural Research and Development, NEIKER- Basque Research and Technology Alliance (BRTA), (Derio) Bizkaia, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nelguezabal@neiker.eus
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Mycobacterium avium subsp. paratuberculosis (Map) is the underlying pathogen causing bovine paratuberculosis (PTB), an enteric granulomatous disease that mainly affects ruminants and for which an effective treatment is needed. Macrophages are the primary target cells for Map, which survives and replicates intracellularly by inhibiting phagosome maturation. Neutrophils are present at disease sites during the early stages of the infection, but seem to be absent in the late stage, in contrast to healthy tissue. Although neutrophil activity has been reported to be impaired following Map infection, their role in PTB pathogenesis has not been fully defined. Neutrophils are capable of releasing extracellular traps consisting of extruded DNA and proteins that immobilize and kill microorganisms, but this mechanism has not been evaluated against Map. Our main objective was to study the interaction of neutrophils with macrophages during an in vitro mycobacterial infection. For this purpose, neutrophils and macrophages from the same animal were cultured alone or together in the presence of Map or Mycobacterium bovis Bacillus-Calmette-Guérin (BCG). Extracellular trap release, mycobacteria killing as well as IL-1β and IL-8 release were assessed. Neutrophils released extracellular traps against mycobacteria when cultured alone and in the presence of macrophages without direct cell contact, but resulted inhibited in direct contact. Macrophages were extremely efficient at killing BCG, but ineffective at killing Map. In contrast, neutrophils showed similar killing rates for both mycobacteria. Co-cultures infected with Map showed the expected killing effect of combining both cell types, whereas co-cultures infected with BCG showed a potentiated killing effect beyond the expected one, indicating a potential synergistic cooperation. In both cases, IL-1β and IL-8 levels were lower in co-cultures, suggestive of a reduced inflammatory reaction. These data indicate that cooperation of both cell types can be beneficial in terms of decreasing the inflammatory reaction while the effective elimination of Map can be compromised. These results suggest that neutrophils are effective at Map killing and can exert protective mechanisms against Map that seem to fail during PTB disease after the arrival of macrophages at the infection site.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Improved version of the manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted February 22, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Bovine neutrophils release extracellular traps and cooperate with macrophages in Mycobacterium avium subsp. paratuberculosis clearance in vitro
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Bovine neutrophils release extracellular traps and cooperate with macrophages in Mycobacterium avium subsp. paratuberculosis clearance in vitro
I Ladero-Auñon, E Molina, A Holder, J Kolakowski, H Harris, A Urkitza, J Anguita, D Werling, N Elguezabal
bioRxiv 2020.12.30.424791; doi: https://doi.org/10.1101/2020.12.30.424791
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Bovine neutrophils release extracellular traps and cooperate with macrophages in Mycobacterium avium subsp. paratuberculosis clearance in vitro
I Ladero-Auñon, E Molina, A Holder, J Kolakowski, H Harris, A Urkitza, J Anguita, D Werling, N Elguezabal
bioRxiv 2020.12.30.424791; doi: https://doi.org/10.1101/2020.12.30.424791

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2548)
  • Biochemistry (4995)
  • Bioengineering (3502)
  • Bioinformatics (15288)
  • Biophysics (6932)
  • Cancer Biology (5431)
  • Cell Biology (7782)
  • Clinical Trials (138)
  • Developmental Biology (4564)
  • Ecology (7184)
  • Epidemiology (2059)
  • Evolutionary Biology (10261)
  • Genetics (7540)
  • Genomics (9835)
  • Immunology (4903)
  • Microbiology (13308)
  • Molecular Biology (5169)
  • Neuroscience (29596)
  • Paleontology (203)
  • Pathology (842)
  • Pharmacology and Toxicology (1470)
  • Physiology (2155)
  • Plant Biology (4788)
  • Scientific Communication and Education (1015)
  • Synthetic Biology (1343)
  • Systems Biology (4025)
  • Zoology (772)