Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism
| Autor: | Andres Baena, Jorge Botero, Maria M. Zorro, Carmen E. Bernal, Jelver Sierra, Katherine Gilchrist, José R. Ramírez-Pineda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) CD4-Positive T-Lymphocytes Naive T cell T cell Immunology lcsh:QR1-502 Dendritic cell differentiation CD8-Positive T-Lymphocytes Lymphocyte Activation Microbiology lcsh:Microbiology Interleukin-12 Subunit p35 03 medical and health sciences Encephalitozoon intestinalis Interferon-gamma Mice 0302 clinical medicine medicine Animals dendritic cells CD40 Antigens Cells Cultured Original Research Immune Evasion CD86 Spores Bacterial MHC class II IL-6 Mice Inbred BALB C CD40 biology Interleukin-6 Encephalitozoon Cell Differentiation Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure IL-12 biology.protein Interleukin 12 microsporidia Encephalitozoonosis B7-2 Antigen CD8 030215 immunology |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Vol 6 (2016) |
| ISSN: | 2235-2988 |
| Popis: | Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNg, CD4+ and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1b or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naive T cell proliferation and IL-2 and IFNg secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNg secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development towards cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation. |
| Databáze: | OpenAIRE |
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