Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells
The gut mucosa is continuously exposed to a vast community of microorganisms, collectively defined as microbiota, establishing a mutualistic relationship with the host and contributing to shape the immune system. Gut microbiota is acquired at birth, and its composition is relatively stable during th...
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doaj-aa28cdc59f154fb79b0c777ffe9f53842020-11-24T22:25:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-02-01510.3389/fmed.2018.00021334642Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T CellsClaudia Burrello0Claudia Burrello1Federica Garavaglia2Fulvia Milena Cribiù3Giulia Ercoli4Silvano Bosari5Flavio Caprioli6Flavio Caprioli7Federica Facciotti8Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology, Milan, ItalyPathology Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan, ItalyPathology Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan, ItalyPathology Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan, ItalyGastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology, Milan, ItalyThe gut mucosa is continuously exposed to a vast community of microorganisms, collectively defined as microbiota, establishing a mutualistic relationship with the host and contributing to shape the immune system. Gut microbiota is acquired at birth, and its composition is relatively stable during the entire adult life. Intestinal dysbiosis, defined as a microbial imbalance of gut bacterial communities, can be caused by several factors, including bacterial infections and antibiotic use, and has been associated with an increased risk to develop or exacerbate immune-mediated pathologies, such as allergic reactions, asthma, and inflammatory bowel diseases. Still, the mechanisms by which antibiotic-induced gut dysbiosis may lead to development of mucosal inflammation are still matter of debate. To this end, we aimed to evaluate the impact of antibiotic treatment on phenotype and functions of intestinal immune cell populations, including invariant natural killer T (iNKT) cells, a subset of lipid-specific T cells profoundly influenced by alterations on the commensal microbiota. To this aim, a cocktail of broad-spectrum antibiotics was administered for 2 weeks to otherwise healthy mice before re-colonization of the intestinal microbial community with oral gavage of eubiotic or dysbiotic mucosa-associated bacteria and luminal colonic content, followed or not by intestinal inflammation induction. Here. we showed that short-term antibiotic treatment alters frequency and functions of intestinal iNKT cells, even in the absence of intestinal inflammation. The presence of a dysbiotic microbiota after antibiotic treatment imprints colonic iNKT and CD4+ T cells toward a pro-inflammatory phenotype that collectively contributes to aggravate intestinal inflammation. Nonetheless, the inflammatory potential of the dysbiotic microbiota decreases over time opening the possibility to temporally intervene on the microbial composition to re-equilibrate dysbiosis, thus controlling concomitantly mucosal immune T cell activations.http://journal.frontiersin.org/article/10.3389/fmed.2018.00021/fulliNKT cellsantibioticsmicrobiotaT cellsintestinal inflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Claudia Burrello Claudia Burrello Federica Garavaglia Fulvia Milena Cribiù Giulia Ercoli Silvano Bosari Flavio Caprioli Flavio Caprioli Federica Facciotti |
spellingShingle |
Claudia Burrello Claudia Burrello Federica Garavaglia Fulvia Milena Cribiù Giulia Ercoli Silvano Bosari Flavio Caprioli Flavio Caprioli Federica Facciotti Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells Frontiers in Medicine iNKT cells antibiotics microbiota T cells intestinal inflammation |
author_facet |
Claudia Burrello Claudia Burrello Federica Garavaglia Fulvia Milena Cribiù Giulia Ercoli Silvano Bosari Flavio Caprioli Flavio Caprioli Federica Facciotti |
author_sort |
Claudia Burrello |
title |
Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells |
title_short |
Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells |
title_full |
Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells |
title_fullStr |
Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells |
title_full_unstemmed |
Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic Invariant Natural Killer T and Conventional CD4+ T Cells |
title_sort |
short-term oral antibiotics treatment promotes inflammatory activation of colonic invariant natural killer t and conventional cd4+ t cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2018-02-01 |
description |
The gut mucosa is continuously exposed to a vast community of microorganisms, collectively defined as microbiota, establishing a mutualistic relationship with the host and contributing to shape the immune system. Gut microbiota is acquired at birth, and its composition is relatively stable during the entire adult life. Intestinal dysbiosis, defined as a microbial imbalance of gut bacterial communities, can be caused by several factors, including bacterial infections and antibiotic use, and has been associated with an increased risk to develop or exacerbate immune-mediated pathologies, such as allergic reactions, asthma, and inflammatory bowel diseases. Still, the mechanisms by which antibiotic-induced gut dysbiosis may lead to development of mucosal inflammation are still matter of debate. To this end, we aimed to evaluate the impact of antibiotic treatment on phenotype and functions of intestinal immune cell populations, including invariant natural killer T (iNKT) cells, a subset of lipid-specific T cells profoundly influenced by alterations on the commensal microbiota. To this aim, a cocktail of broad-spectrum antibiotics was administered for 2 weeks to otherwise healthy mice before re-colonization of the intestinal microbial community with oral gavage of eubiotic or dysbiotic mucosa-associated bacteria and luminal colonic content, followed or not by intestinal inflammation induction. Here. we showed that short-term antibiotic treatment alters frequency and functions of intestinal iNKT cells, even in the absence of intestinal inflammation. The presence of a dysbiotic microbiota after antibiotic treatment imprints colonic iNKT and CD4+ T cells toward a pro-inflammatory phenotype that collectively contributes to aggravate intestinal inflammation. Nonetheless, the inflammatory potential of the dysbiotic microbiota decreases over time opening the possibility to temporally intervene on the microbial composition to re-equilibrate dysbiosis, thus controlling concomitantly mucosal immune T cell activations. |
topic |
iNKT cells antibiotics microbiota T cells intestinal inflammation |
url |
http://journal.frontiersin.org/article/10.3389/fmed.2018.00021/full |
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