Lkb1 plays an important role in regulating glucose homeostasis and energy metabolism. In addition, there is also evidence that has highlighted a prominent role for Lkb1 in the function of macrophages. Lkb1 inhibits the activation and inflammatory function of innate macrophages. It was found that disruption of Lkb1 impaired the self-renewal of AMs, contributing to the reduction of AMs, which led to aggravated symptoms and EXCESSIVE accumulation of NEUTROPHILS in Staphylococcus aureus (S. aureus) pneumonia and ASTHMA. In addition, we found that many critical immune genes of AMs are regulated by Lkb1. Transcriptomic sequencing also revealed that Lkb1 inhibits proinflammatory pathways, including IL-17 signaling and neutrophil migration pathways. The increased expression of inflammatory mediators in Lkb1-deficient AMs might contribute to the more severe pathology in Cd11cCreLkb1f/f mice during S. aureus infection and allergic inflammation.