2. Academic Validation
  3. Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2

Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2

  • Nat Microbiol. 2016 Apr 25;1(6):16054. doi: 10.1038/nmicrobiol.2016.54.
Kouyuki Hirayasu 1,  Fumiji Saito 2,  Tadahiro Suenaga 1 2,  Kyoko Shida 1,  Noriko Arase 2 3,  Keita Oikawa 4,  Toshifumi Yamaoka 3,  Hiroyuki Murota 3,  Hiroji Chibana 5,  Ichiro Nakagawa 6,  Tomoko Kubori 7,  Hiroki Nagai 7,  Yuji Nakamaru 8,  Ichiro Katayama 3,  Marco Colonna 9,  Hisashi Arase 1 2
Affiliations

Affiliations

  • 1 Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
  • 2 Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
  • 3 Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
  • 4 Department of Otolaryngology, Tenshi Hospital, Sapporo, Japan.
  • 5 Medical Mycology Research Center, Chiba University, Chuo-ku, Chiba 260-8673, Japan.
  • 6 Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
  • 7 Laboratory of Combined Research on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
  • 8 Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
  • 9 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
PMID: 27572839 DOI: 10.1038/nmicrobiol.2016.54
Abstract

Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why Microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with Bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens.

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