Autophagy links antimicrobial activity with antigen presentation in Langerhans cells
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
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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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 1

IFN-γ induces antimicrobial activity in Langerhans cells.

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IFN-γ induces antimicrobial activity in Langerhans cells. (A) IFN-γ expr...
(A) IFN-γ expression in leprosy lesions, tuberculoid (T-lep), and lepromatous (L-lep); 1 representative labeled section is shown out of 4 individuals at 20×. Scale bar: 30 μm. (B) Ratio of IFN-γ and nuclear staining quantified by ImmunoRatio. Data are represented as mean ± SEM, n = 6 IHC sections. (C) Colocalization of IFN-γ (green) and CD1a (red) in T-lep lesions. Data are representative of 3 individual T-lep or L-lep lesions at 63×. (D) Human LCDC were stimulated with recombinant IFN-γ for 4 hours, washed and infected with M. leprae at a MOI of 10 overnight, and washed and stimulated with rIFN-γ for an additional 4 days. Viability of M. leprae was calculated by the ratio of bacterial 16S RNA and DNA (RLEP) detected by qPCR, and percent increase or decrease relative to no treatment (media) was determined. Data are represented as mean ± SEM, n = 9. (E) Human primary CD1a+ epidermal cells or (F) CD1a– epidermal cells were stimulated with rIFN-γ for 4 hours and washed and infected with M. leprae as in D. Viability of M. leprae was calculated as described in D. Data are represented as mean ± SEM, n = 5. *P < 0.05, **P < 0.01. Two-tailed Student’s t test.