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
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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