Leukocyte associated immunoglobulin-like receptor 1 modulates immune response to <i>Staphylococcus aureus</i>infection

Abstract Immunity is a balance of maximal pathogen defense with minimal host damage. Inhibitory immune receptors are important for maintaining this balance. We recently identified elevated levels leukocyte-associated immunoglobulin (Ig)-like receptor protein1 (LAIR1), an inhibitory receptor, in cutaneous lymphoma patients, whom invasive Staphylococcus aureus (S. aureus) infections frequent. therefore tested Lair1 knock-out (KO) mice two models S. infection: pneumonia and subcutaneous skin infection. In WT mice, resolve by 14 days post-infection (dpi), while cause &amp;gt;50% lethality 2dpi. both models, KO showed consistent patterns myeloid hyper-activation. had consistently larger lesions than throughout the days, but no difference bacterial clearance. higher survival (100% vs. 33% WT) despite comparable measures lung injury cell recruitment. produced proinflammatory cytokines (IL-6, IL-1b) neutrophil chemokines (CCL2, 3, 4) lung, bronchoalveolar lavage, multiplex cytokine array. bone marrow-derived macrophages infected vitro also secreted (IL-6) 4). Together, our results demonstrate that LAIR1 loss enhances activation, resulting excessive tissue damage infection, yet protective against death pneumonia. posit plays crucial role balancing response; activity can be beneficial or detrimental to depending on site type