PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan

Takashi Kaneko^1, 5, Tamaki Yano², Kamna Aggarwal¹, Jae-Hong Lim³, Kazunori Ueda², Yoshiteru Oshima², Camilla Peach¹, Deniz Erturk-Hasdemir¹, William E Goldman⁴, Byung-Ha Oh³, Shoichiro Kurata² & Neal Silverman¹

¹  Division of Infectious Disease, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

²  Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.

³  Center for Biomolecular Recognition and Division of Molecular and Life Science, Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea.

⁴  Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

⁵  Department of Periodontology, Nagasaki University School of Dentistry, Nagasaki, 852-8588, Japan.

Drosophila rely entirely on an innate immune response to combat microbial infection. Diaminopimelic acid–containing peptidoglycan, produced by Gram-negative bacteria, is recognized by two receptors, PGRP-LC and PGRP-LE, and activates a homolog of transcription factor NF-B through the Imd signaling pathway. Here we show that full-length PGRP-LE acted as an intracellular receptor for monomeric peptidoglycan, whereas a version of PGRP-LE containing only the PGRP domain functioned extracellularly, like the mammalian CD14 molecule, to enhance PGRP-LC-mediated peptidoglycan recognition on the cell surface. Interaction with the imd signaling protein was not required for PGRP-LC signaling. Instead, PGRP-LC and PGRP-LE signaled through a receptor-interacting protein homotypic interaction motif–like motif. These data demonstrate that like mammals, drosophila use both extracellular and intracellular receptors, which have conserved signaling mechanisms, for innate immune recognition.

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