PMID- 33936099 OWN - NLM STAT- MEDLINE DCOM- 20211014 LR - 20211014 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Chlamydia trachomatis Infection Impairs MHC-I Intracellular Trafficking and Antigen Cross-Presentation by Dendritic Cells. PG - 662096 LID - 10.3389/fimmu.2021.662096 [doi] LID - 662096 AB - 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. CI - Copyright (c) 2021 Del Balzo, Capmany, Cebrian and Damiani. FAU - Del Balzo, Diego AU - Del Balzo D AD - Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Mendoza, Argentina. FAU - Capmany, Anahi AU - Capmany A AD - Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Mendoza, Argentina. FAU - Cebrian, Ignacio AU - Cebrian I AD - Instituto de Histologia y Embriologia de Mendoza (IHEM)-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cuyo, Mendoza, Argentina. FAU - Damiani, Maria Teresa AU - Damiani MT AD - Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Mendoza, Argentina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210415 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Animals MH - Antigen Presentation/*immunology MH - Bone Marrow Cells/immunology MH - Cell Line MH - Chlamydia trachomatis/*immunology/pathogenicity MH - Cross-Priming/*immunology MH - Dendritic Cells/*immunology/*microbiology MH - Endocytosis MH - Histocompatibility Antigens Class I/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Protein Transport PMC - PMC8082151 OTO - NOTNLM OT - Chlamydia trachomatis OT - MHC-I recycling OT - cross-presentation OT - dendritic cells OT - endocytic recycling compartment COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/04 06:00 MHDA- 2021/10/15 06:00 PMCR- 2021/01/01 CRDT- 2021/05/03 06:12 PHST- 2021/01/31 00:00 [received] PHST- 2021/03/26 00:00 [accepted] PHST- 2021/05/03 06:12 [entrez] PHST- 2021/05/04 06:00 [pubmed] PHST- 2021/10/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.662096 [doi] PST - epublish SO - Front Immunol. 2021 Apr 15;12:662096. doi: 10.3389/fimmu.2021.662096. eCollection 2021.