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Med Microbiol Immunol. 2017 Apr;206(2):111-123. doi: 10.1007/s00430-016-0488-4. Epub 2016 Dec 16.

Using dendritic cells to evaluate how Burkholderia cenocepacia clonal isolates from a chronically infected cystic fibrosis patient subvert immune functions.

Author information

1
Centro de Estudos de Doenças Crónicas, CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
2
Faculdade de Engenharia, Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal.
3
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
4
UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.
5
iBB-Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
6
Centro de Estudos de Doenças Crónicas, CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal. p.videira@fct.unl.pt.
7
UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. p.videira@fct.unl.pt.
8
CDG & Allies - Professionals and Patient Associations International Network (CDG & Allies - PPAIN), Caparica, Portugal. p.videira@fct.unl.pt.

Abstract

Infection with Burkholderia cepacia complex (Bcc) bacteria is a threat to cystic fibrosis (CF) patients, commonly leading to a fatal pneumonia, the cepacia syndrome. It causes a massive production of pro-inflammatory cytokines and leucocyte recruitment to airway epithelium without resolving infection and contributing to tissue lesion. To dissect how Bcc bacteria subvert the immune response, we developed a co-culture model with human dendritic cells (DCs) and B. cenocepacia clonal variants isolated from a chronically infected CF patient, who died with cepacia syndrome. We demonstrated that the two late variants were sevenfold and 17-fold (respectively) more internalized by DCs than the variant that initiated infection. The late variants showed improved survival within DCs (60.29 and 52.82 CFU/DC) compared to the initial variant (0.38 CFU/DC). All clonal isolates induced high expression of inflammatory cytokines IL-8, IL-6, IL-1β, IL-12, IL-23, TNF-α and IL-1β. This pro-inflammatory trait was significantly more pronounced in DCs infected with the late variants than in DCs infected with the variant that initiated patient's infection. All infected DCs failed to upregulate maturation markers, HLA-DR, CD80, CD86 and CD83. Nevertheless, these infected DCs activated approximately twice more T cells than non-infected DCs. Similar T cell activation was observable with respective conditioned media, suggesting a non-antigen-specific activation. Our data indicate that during prolonged infection, B. cenocepacia acquires ability to survive intracellularly, inducing inflammation, while refraining DC's maturation and stimulating non-antigen-specific T cell responses. The co-culture model here developed may be broadly applied to study B. cenocepacia-induced immunomodulation.

KEYWORDS:

Burkholderia cenocepacia; Clonal isolates; Cystic fibrosis; Dendritic cells; Immune escape; Maturation

PMID:
27987042
DOI:
10.1007/s00430-016-0488-4
[Indexed for MEDLINE]

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