Microbial proteases degrade a variety of host proteins. However, it has remained largely unknown why microbes have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we 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 M. hyorhinis, L. pneumophila, and C. albicans cleaved N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils and induced IL-8 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 the patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptors in the host immune system to detect immunoglobulin abnormalities caused by microbial pathogens.