Autophagy links antimicrobial activity with antigen presentation in Langerhans cells
Angeline Tilly Dang, … , Barry R. Bloom, Robert L. Modlin
Angeline Tilly Dang, … , Barry R. Bloom, Robert L. Modlin
Published April 18, 2019
Citation Information: JCI Insight. 2019;4(8):e126955. https://doi.org/10.1172/jci.insight.126955.
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Research Article Immunology Infectious disease

Autophagy links antimicrobial activity with antigen presentation in Langerhans cells

Abstract

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.

Authors

Angeline Tilly Dang, Rosane M.B. Teles, Phillip T. Liu, Aaron Choi, Annalisa Legaspi, Euzenir N. Sarno, Maria T. Ochoa, Kislay Parvatiyar, Genhong Cheng, Michel Gilliet, Barry R. Bloom, Robert L. Modlin

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Figure 5

The role of autophagy in Langerhans cells.

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The role of autophagy in Langerhans cells. (A) Human LCDC were stimulate...
(A) Human LCDC were stimulated with rIFN-γ for 4 hours, washed, and infected with M. leprae at a MOI of 10 overnight; washed and stimulated with rIFN-γ, with or without blocking anti-CD1a; and cultured with CD4+ T cells LCDC4.G, which were isolated from a T-lep lesion. T cells were pulsed with 3H-thymidine after 4 days of culture. Cells were harvested, and 3H incorporation was measured by a scintillation counter. Data are represented as mean ± SEM of triplicate cultures, n = 6. (B) CD4+ TRM cells secreted IFN-γ upon activation. CD4+ T cells (LCD4.G) were stimulated overnight by CD3/CD28 DynaBeads (TAct) or cultured in media alone (TRest), supernatants were collected, and IFN-γ was measured by sandwich ELISA. Data are represented as mean ± SEM, n = 4. (C) Human LCDC were cultured with T cell supernatants (TRest and TAct) in the presence or absence of an IFN-γ blocking mAb or isotype control antibody in 10% human vitamin D–sufficient serum. Cathelicidin gene expression was assessed by qPCR. Data are represented as mean fold change ± SEM, n = 3. *P < 0.05, **P < 0.01. Two-tailed Student’s t test or repeated measures 1-way ANOVA.