Autophagy links antimicrobial activity with antigen presentation in Langerhans cells
Autor: | Kislay Parvatiyar, Robert L. Modlin, Euzenir Nunes Sarno, Barry R. Bloom, Genhong Cheng, Rosane M. B. Teles, Philip T. Liu, Maria Teresa Ochoa, Annalisa Legaspi, Aaron Choi, Angeline Tilly Dang, Michel Gilliet |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_treatment T-Lymphocytes Biopsy Cathelicidin 0302 clinical medicine 2.1 Biological and endogenous factors Pathogen Mycobacterium leprae Cells Cultured Phagosome Antigen Presentation Microscopy Infectious disease Cultured biology Bacterial General Medicine Recombinant Proteins Up-Regulation medicine.anatomical_structure Infectious Diseases 030220 oncology & carcinogenesis Infection Research Article T cell Cells Antigen presentation Primary Cell Culture Immunology Electron Microbiology 03 medical and health sciences Interferon-gamma Microscopy Electron Transmission Antigen Cathelicidins Leprosy medicine Autophagy Humans Transmission Antigens Antigens Bacterial Autophagosomes biology.organism_classification 030104 developmental biology Langerhans Cells Epidermis Lysosomes Antimicrobial Cationic Peptides |
Zdroj: | JCI insight, vol 4, iss 8 Dang, Angeline Tilly; Teles, Rosane Mb; Liu, Phillip T; Choi, Aaron; Legaspi, Annalisa; Sarno, Euzenir N; et al.(2019). Autophagy links antimicrobial activity with antigen presentation in Langerhans cells.. JCI insight, 4(8). doi: 10.1172/jci.insight.126955. UCLA: Retrieved from: http://www.escholarship.org/uc/item/6584h5s6 |
Popis: | DC, through the uptake, processing, and presentation of antigen, are responsible for activation of T cell responses to defend the host against infection, yet it is not known if they can directly kill invading bacteria. Here, we studied in human leprosy, how Langerhans cells (LC), specialized DC, contribute to host defense against bacterial infection. IFN-γ treatment of LC isolated from human epidermis and infected with Mycobacterium leprae (M. leprae) activated an antimicrobial activity, which was dependent on the upregulation of the antimicrobial peptide cathelicidin and induction of autophagy. IFN-γ induction of autophagy promoted fusion of phagosomes containing M. leprae with lysosomes and the delivery of cathelicidin to the intracellular compartment containing the pathogen. Autophagy enhanced the ability of M. leprae-infected LC to present antigen to CD1a-restricted T cells. The frequency of IFN-γ labeling and LC containing both cathelicidin and autophagic vesicles was greater in the self-healing lesions vs. progressive lesions, thus correlating with the effectiveness of host defense against the pathogen. These data indicate that autophagy links the ability of DC to kill and degrade an invading pathogen, ensuring cell survival from the infection while facilitating presentation of microbial antigens to resident T cells. |
Databáze: | OpenAIRE |
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