RRC ID 51715
Author Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nakagawa I, Kubori T, Nagai H, Nakamaru Y, Katayama I, Colonna M, Arase H.
Title Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2.
Journal Nat Microbiol
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.
Volume 1(6)
Pages 16054
Published 2016-4-25
DOI 10.1038/nmicrobiol.2016.54
PII nmicrobiol201654
PMID 27572839
MeSH Animals Bacteria / enzymology* Bacteria / metabolism Cytokines / metabolism Humans Immunity, Innate Immunoglobulins / metabolism* Immunoglobulins / pharmacology Legionella pneumophila / drug effects Legionella pneumophila / enzymology Legionella pneumophila / growth & development Legionella pneumophila / immunology Legionnaires' Disease Mice Monocytes / drug effects Monocytes / microbiology Mycoplasma hyorhinis / enzymology Neutrophils / drug effects Peptide Hydrolases / metabolism* Receptors, Immunologic / immunology* Receptors, Immunologic / metabolism Streptococcus pneumoniae / enzymology
IF 15.54
Times Cited 12
Human and Animal Cells 293T(RCB2202)