Chlamydia trachomatis Infection Impairs MHC-I Intracellular Trafficking and Antigen Cross-Presentation by Dendritic Cells

Abstract

During cross-presentation, exogenous antigens (i.e. intracellular pathogens or tumor cells) are internalized and processed within the endocytic system and also by the proteasome in the cytosol. Then, antigenic peptides are associated with Major Histocompatibility Complex (MHC) class I molecules and these complexes transit to the plasma membrane in order to trigger cytotoxic immune responses through the activation of CD8+ T lymphocytes. Dendritic cells (DCs) are particularly adapted to achieve efficient antigen cross-presentation and their endocytic network displays important roles during this process, including a sophisticated MHC-I transport dependent on recycling compartments. In this study, we show that C. trachomatis, an obligate intracellular pathogen that exhibits multiple strategies to evade the immune system, is able to induce productive infections in the murine DC line JAWS-II. Our results show that when C. trachomatis infects these cells, the bacteria-containing vacuole strongly recruits host cell recycling vesicles, but no other endosomal compartments. Furthermore, we found that chlamydial infection causes significant alterations of MHC-I trafficking in JAWS-II DCs: reduced levels of MHC-I expression at the cell surface, disruption of the perinuclear MHC-I intracellular pool, and impairment of MHC-I endocytic recycling to the plasma membrane. We observed that all these modifications lead to a hampered cross-presentation ability of soluble and particulate antigens by JAWS-II DCs and primary bone marrow-derived DCs. In summary, our findings provide substantial evidence that C. trachomatis hijacks the DC endocytic recycling system, causing detrimental changes on MHC-I intracellular transport, which are relevant for competent antigen cross-presentation.

HSV-1 Infection of Epithelial Dendritic Cells Is a Critical Strategy for Interfering with Antiviral Immunity

“…In this case, in the event that viruses or the antibody binding to HVEM lead to a pro-inflammatory reaction of dendritic cells, including a higher expression of the IFN-α, IFN-β, and IFN-γ in groups of virus infection and adding antibodies of HVEM than those in group of adding antibody of gD, it should be understandable during post infection, as while higher expression of GM-CSF, TNF-α, TGF-β, IL-4 and IL-6 was found at 48 h after infection ( Figure 1 C). The upregulation of some surface markers of dendritic cell maturation, such as CD83 and MHC-I [ 20 , 21 , 22 ], was also observed in virus-infected JAWSII-dendritic cells compared with antibody-blocking cells ( Figure 1 D). These results show that HSV-1 enables the infection of dendritic cells via the interaction between gD and HVEM, followed by viral replication.…”

Heterologous prime-boost vaccination based on Polymorphic protein D protects against intravaginal Chlamydia trachomatis infection in mice

“…As., Argentina); and, a green fluorescent Ct L2 strain harboring p2TK2-SW2 IncDProm-RSGFP-IncDTerm serovar L2 (GFP- Ct ) kindly provided by Derré 50 . Bacteria were propagated in HeLa 229 or McCoy cells, harvested, purified, and quantified as previously described by Del Balzo et al 51 . HeLa cells (ABAC, Argentina) were cultured in high glucose Dulbecco´s Modified Eagle´s Medium (GIBCO, Thermo Fisher Scientific, Argentina) supplemented with 10% (v/v) fetal bovine serum (FBS) (Internegocios SA, Argentina), 0.3 mg/mL l -glutamine (ICN Biomedicals Inc) and 1.55 mg/mL glucose (Biopack, Argentina) without antibiotics in 5% CO2 at 37 °C.…”

Targeting FGL2 in glioma immunosuppression and malignant progression

“…Once found, DCs immediately function to engulf these antigens and cells while digesting them with digestive enzymes from intracellular lysosomes. Digested foreign bodies and cells leave behind fragments of biomolecules that DCs will put on MHC molecules on the cell surface and enter the lymphoid tissue for T cell recognition ( 47 – 49 ).. In this process, DC cells are gradually transformed into mature antigen-presenting cells, a process often referred to as “antigen presentation”.…”