title: Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism.
abstract: 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, IFNγ, 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-1β 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 naïve T cell proliferation and IL-2 and IFNγ secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNγ secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development toward 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.
authors: Grupo Inmunomodulación, Universidad de AntioquiaMedellín, Colombia; Grupo de Parasitología, Universidad de AntioquiaMedellín, Colombia.
authors: Carmen E
authors: CE
authors: Bernal
authors: Grupo Inmunomodulación, Universidad de Antioquia Medellín, Colombia.
authors: Maria M
authors: MM
authors: Zorro
authors: Grupo Inmunomodulación, Universidad de Antioquia Medellín, Colombia.
authors: Jelver
authors: J
authors: Sierra
authors: Grupo Inmunomodulación, Universidad de Antioquia Medellín, Colombia.
authors: Katherine
authors: K
authors: Gilchrist
authors: Grupo de Parasitología, Universidad de Antioquia Medellín, Colombia.
authors: Jorge H
authors: JH
authors: Botero
authors: Grupo de Inmunología Celular e Inmunogenética, Universidad de AntioquiaMedellín, Colombia; Departamento de Microbiología y Parasitología, Universidad de AntioquiaMedellín, Colombia.
authors: Andres
authors: A
authors: Baena
authors: Grupo Inmunomodulación, Universidad de AntioquiaMedellín, Colombia; Corporación Académica para el Estudio de Patologías Tropicales, Facultad de Medicina, Universidad de AntioquiaMedellín, Colombia.
authors: Jose R
authors: JR
authors: Ramirez-Pineda
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D016819:Encephalitozoon / Q000276:immunology*; D016890:Encephalitozoonosis / Q000276:immunology* / Q000382:microbiology; D057131:Immune Evasion / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053765:Interleukin-12 Subunit p35 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013171:Spores, Bacterial / Q000276:immunology
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; C508859:Il12a protein, mouse; D053765:Interleukin-12 Subunit p35; D015850:Interleukin-6; D007371:Interferon-gamma
keywords: Encephalitozoon intestinalis; IL-12; IL-6; dendritic cells; microsporidia