Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to
infection. Inflammatory monocytes are recruited to both the
infection site and vital organs during
sepsis; however, the mechanisms that orchestrate their migration, as well as the participation of these cells in systemic
inflammation and vital organ damage, are still not fully elucidated. In this context, we described that CCR2-deficient mice had diminished migration of inflammatory monocytes from bone marrow to the circulation and subsequently to the site of
infection and vital organs during cecal
ligation and
puncture (CLP)-induced polymicrobial
sepsis. The reduction in the migration of inflammatory monocytes to the
infection site was accompanied by a significant increase in the number of neutrophils in the same compartment, which seemed to counterbalance the absence of inflammatory monocytes in controlling microbial growth. Indeed, wild-type (WT) and CCR2-deficient mice under CLP presented similar control of
infection. However, the CCR2-deficient mice were more resistant to
sepsis, which was associated with a decrease in inflammatory mediators and organ damage
biomarkers. Furthermore, the systemic adoptive transfer of CCR2-WT or CCR2-deficient inflammatory monocytes into CCR2-deficient mice equally increased the susceptibility to
sepsis, demonstrating the deleterious role of these cells in the periphery even when CCR2 is absent. Thus, despite the host-protective role of inflammatory monocytes in controlling
infection, our results demonstrated that the mechanism by which CCR2 deficiency shows protection to CLP-induced
sepsis is due to a decrease of inflammatory monocytes emigration from bone marrow to the circulation and vital organs, resulting in the reduction of organ damage and systemic
cytokine production.