Microbial proteases degrade a variety of host proteins. In Nature Microbiology, Arase and colleagues show that immunoglobulins cleaved by microbial proteases are detected specifically by the activating receptor LILRA2, which is expressed by myeloid cells. LILRA2 specifically recognizes N-terminally truncated human immunoglobulin M (IgM) and IgG, but not cleaved IgA, and binds to hidden or altered structures in the immunoglobulin light chain exposed by cleavage of the heavy chain. Various microbial pathogens, but not commensal bacteria, cleave human IgM and IgG, and proteases from different microbial pathogens show different immunoglobulin-cleavage patterns. LILRA2-dependent cleaved-immunoglobulin signaling induces IL-8 expression and inhibits the growth of Legionella pneumophila in human myeloid cells. Cleaved immunoglobulins are detected in the pus of patients with bacterial infection. The candidate mouse homologs of LILRA, the PIR-A receptors, do not recognize microbially cleaved IgM, and thus the functional mouse homolog of LILRA2 remains unknown.

Nat. Microbiol. (25 April 2016) doi:10.1038/nmicrobiol.2016.54