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Biofilm-dispersed pneumococci induce elevated leukocyte and platelet activation

Chao, Yashuan LU ; Mørch, Martina LU ; Håkansson, Anders P LU orcid and Shannon, Oonagh LU (2024) In Frontiers in cellular and infection microbiology 14. p.1-14
Abstract

INTRODUCTION: Streptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using ex vivo stimulation of whole blood and... (More)

INTRODUCTION: Streptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using ex vivo stimulation of whole blood and platelet-rich plasma with pneumococcal populations representing distinct stages of the infectious process (biofilm bacteria and dispersed bacteria) as well as conventional broth-grown culture (planktonic bacteria).

METHODS: Flow cytometry and ELISA were used to assess surface and soluble activation markers for neutrophil and monocyte activation, platelet-neutrophil complex and platelet-monocyte complex formation, and platelet activation and responsiveness.

RESULTS: Overall, we found that biofilm-derived bacteria (biofilm bacteria and dispersed bacteria) induced significant activation of neutrophils, monocytes, and platelets. In contrast, little to no activation was induced by planktonic bacteria. Platelets remained functional after stimulation with bacterial populations and the degree of responsiveness was inversely related to initial activation. Bacterial association with immune cells followed a similar pattern as activation.

DISCUSSION: Differences in activation of and association with immune cells by biofilm-derived populations could be an important consideration for other pathogens that have a biofilm state. Gaining insight into how these bacterial populations interact with the host immune response may reveal immunomodulatory targets to interfere with disease development.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biofilms/growth & development, Humans, Streptococcus pneumoniae/immunology, Platelet Activation, Neutrophils/immunology, Monocytes/immunology, Pneumococcal Infections/microbiology, Blood Platelets/microbiology, Leukocytes/immunology, Flow Cytometry, Adult, Female, Male
in
Frontiers in cellular and infection microbiology
volume
14
article number
1405333
pages
1 - 14
publisher
Frontiers Media S. A.
external identifiers
  • pmid:39149421
  • scopus:85201421085
ISSN
2235-2988
DOI
10.3389/fcimb.2024.1405333
language
English
LU publication?
yes
additional info
Copyright © 2024 Chao, Mørch, Håkansson and Shannon.
id
ee7171c3-243a-4c0c-bd78-2a971c56bcb0
date added to LUP
2024-09-09 12:49:51
date last changed
2024-09-24 05:27:33
@article{ee7171c3-243a-4c0c-bd78-2a971c56bcb0,
  abstract     = {{<p>INTRODUCTION:  Streptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using  ex vivo stimulation of whole blood and platelet-rich plasma with pneumococcal populations representing distinct stages of the infectious process (biofilm bacteria and dispersed bacteria) as well as conventional broth-grown culture (planktonic bacteria). </p><p>METHODS: Flow cytometry and ELISA were used to assess surface and soluble activation markers for neutrophil and monocyte activation, platelet-neutrophil complex and platelet-monocyte complex formation, and platelet activation and responsiveness.</p><p>RESULTS: Overall, we found that biofilm-derived bacteria (biofilm bacteria and dispersed bacteria) induced significant activation of neutrophils, monocytes, and platelets. In contrast, little to no activation was induced by planktonic bacteria. Platelets remained functional after stimulation with bacterial populations and the degree of responsiveness was inversely related to initial activation. Bacterial association with immune cells followed a similar pattern as activation.</p><p>DISCUSSION: Differences in activation of and association with immune cells by biofilm-derived populations could be an important consideration for other pathogens that have a biofilm state. Gaining insight into how these bacterial populations interact with the host immune response may reveal immunomodulatory targets to interfere with disease development.</p>}},
  author       = {{Chao, Yashuan and Mørch, Martina and Håkansson, Anders P and Shannon, Oonagh}},
  issn         = {{2235-2988}},
  keywords     = {{Biofilms/growth & development; Humans; Streptococcus pneumoniae/immunology; Platelet Activation; Neutrophils/immunology; Monocytes/immunology; Pneumococcal Infections/microbiology; Blood Platelets/microbiology; Leukocytes/immunology; Flow Cytometry; Adult; Female; Male}},
  language     = {{eng}},
  pages        = {{1--14}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in cellular and infection microbiology}},
  title        = {{Biofilm-dispersed pneumococci induce elevated leukocyte and platelet activation}},
  url          = {{http://dx.doi.org/10.3389/fcimb.2024.1405333}},
  doi          = {{10.3389/fcimb.2024.1405333}},
  volume       = {{14}},
  year         = {{2024}},
}