The protective role of MDL-1 in sepsis-induced lung injury: insights from a murine CLP model

Our findings demonstrate that MDL-1 deficiency exacerbates lung inflammation in a CLP-induced murine sepsis model. These results underscore the essential immunomodulatory role of MDL-1 in mitigating excessive pulmonary inflammatory responses during sepsis.The Myeloid DAP12-associating lectin-1 (MDL-1) serves as a pivotal pattern recognition receptor crucial for recognizing various pathogenic microorganisms and orchestrating immune responses during infections. In this study, we elucidate that MDL-1 exhibits predominant expression within the mononuclear phagocyte system and plays a significant role in modulating the severity of lung injury in sepsis. Notably, MDL-1-deficient (MDL-1^-/-) mice subjected to cecal ligation and puncture (CLP) exhibited elevated levels of pro-inflammatory cytokines such as IL-6 and TNF-α, along with decreased production of IFN-γ. Moreover, the expression levels of chemokines like IP-10, KC, MCP-1, and MIP-1 were markedly upregulated in septic MDL-1^-/- mice. Concurrently, enhanced levels of Syk and cleaved caspase 3 were detected in the lung tissues of MDL-1^-/--CLP animals, underscoring an augmented inflammatory response. Collectively, our findings indicate that MDL-1 deficiency correlates with the exacerbation of lung inflammation in a murine model of CLP-induced sepsis, highlighting the critical immunomodulatory role of MDL-1 in safeguarding against excessive pulmonary inflammation.