Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation

Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the immune system through pathogen associated molecular pattern (PAMP) receptors (i...

Full description

Saved in:
Bibliographic Details
Main Authors: Amanda Carroll-Portillo, October Barnes, Cristina N. Coffman, Cody A. Braun, Sudha B. Singh, Henry C. Lin
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/17/1/134
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832587260569059328
author Amanda Carroll-Portillo
October Barnes
Cristina N. Coffman
Cody A. Braun
Sudha B. Singh
Henry C. Lin
author_facet Amanda Carroll-Portillo
October Barnes
Cristina N. Coffman
Cody A. Braun
Sudha B. Singh
Henry C. Lin
author_sort Amanda Carroll-Portillo
collection DOAJ
description Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the immune system through pathogen associated molecular pattern (PAMP) receptors (i.e., TLRs). Given that phages reside in the same body niches as bacteria, they share the propensity to stimulate or quench immune responses depending on the nature of their interactions with host immune cells. While most in vitro research focuses on the outcomes of direct application of phages to immune cells of interest, the potential impact of their transcytosis through the intestinal barrier has yet to be considered. As transcytosis through intestinal cells is a necessary step in healthy systems for access by phage to the underlying immune cell populations, it is imperative to understand how this step may play a role in immune activation. We compared the activation of macrophages (as measured by TNFα secretion) following direct phage application to those stimulated by incubation with phage transcytosed through a polarized Caco2 epithelial barrier model. Our results demonstrate that phages capable of activating TNFα secretion upon direct contact maintain the stimulatory capability following transcytosis. Furthermore, activation of macrophages by a transcytosed phage is enhanced as compared to that occurring with an equivalent multiplicity of directly applied phage.
format Article
id doaj-art-009e8c6efc5140f9995592f321d7b016
institution Kabale University
issn 1999-4915
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Viruses
spelling doaj-art-009e8c6efc5140f9995592f321d7b0162025-01-24T13:52:42ZengMDPI AGViruses1999-49152025-01-0117113410.3390/v17010134Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune ActivationAmanda Carroll-Portillo0October Barnes1Cristina N. Coffman2Cody A. Braun3Sudha B. Singh4Henry C. Lin5Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM 87131, USABiomedical Research Institute of New Mexico, Albuquerque, NM 87108, USABiomedical Research Institute of New Mexico, Albuquerque, NM 87108, USABiomedical Research Institute of New Mexico, Albuquerque, NM 87108, USABiomedical Research Institute of New Mexico, Albuquerque, NM 87108, USADivision of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM 87131, USAInteractions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the immune system through pathogen associated molecular pattern (PAMP) receptors (i.e., TLRs). Given that phages reside in the same body niches as bacteria, they share the propensity to stimulate or quench immune responses depending on the nature of their interactions with host immune cells. While most in vitro research focuses on the outcomes of direct application of phages to immune cells of interest, the potential impact of their transcytosis through the intestinal barrier has yet to be considered. As transcytosis through intestinal cells is a necessary step in healthy systems for access by phage to the underlying immune cell populations, it is imperative to understand how this step may play a role in immune activation. We compared the activation of macrophages (as measured by TNFα secretion) following direct phage application to those stimulated by incubation with phage transcytosed through a polarized Caco2 epithelial barrier model. Our results demonstrate that phages capable of activating TNFα secretion upon direct contact maintain the stimulatory capability following transcytosis. Furthermore, activation of macrophages by a transcytosed phage is enhanced as compared to that occurring with an equivalent multiplicity of directly applied phage.https://www.mdpi.com/1999-4915/17/1/134bacteriophagetranscytosismacrophageTNFαT4polarized Caco2
spellingShingle Amanda Carroll-Portillo
October Barnes
Cristina N. Coffman
Cody A. Braun
Sudha B. Singh
Henry C. Lin
Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation
Viruses
bacteriophage
transcytosis
macrophage
TNFα
T4
polarized Caco2
title Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation
title_full Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation
title_fullStr Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation
title_full_unstemmed Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation
title_short Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation
title_sort transcytosis of t4 bacteriophage through intestinal cells enhances its immune activation
topic bacteriophage
transcytosis
macrophage
TNFα
T4
polarized Caco2
url https://www.mdpi.com/1999-4915/17/1/134
work_keys_str_mv AT amandacarrollportillo transcytosisoft4bacteriophagethroughintestinalcellsenhancesitsimmuneactivation
AT octoberbarnes transcytosisoft4bacteriophagethroughintestinalcellsenhancesitsimmuneactivation
AT cristinancoffman transcytosisoft4bacteriophagethroughintestinalcellsenhancesitsimmuneactivation
AT codyabraun transcytosisoft4bacteriophagethroughintestinalcellsenhancesitsimmuneactivation
AT sudhabsingh transcytosisoft4bacteriophagethroughintestinalcellsenhancesitsimmuneactivation
AT henryclin transcytosisoft4bacteriophagethroughintestinalcellsenhancesitsimmuneactivation