Sepsis-typically caused by an uncontrolled and amplified host systemic inflammatory response to microbial
infection-is a life-threatening complex clinical disorder and remains a major cause of
infection-related deaths in the intensive care unit. Emerging evidence suggests that
neuropilin 1 (Nrp1), an originally defined coreceptor for
class 3 semaphorins and
VEGF, plays important roles in the immune system; however, the function and regulation of macrophage Nrp1 in host immune defense against
bacterial infection remain unknown. To address this problem, we generated myeloid cell-specific Nrp1-knockout (Nrp1myel-KO) mice and applied 2 stringent animal models of
sepsis: cecal
ligation and
puncture as well as
intraperitoneal injection of LPS. Here, we reported that myeloid cell-specific Nrp1-deficient mice exhibited enhanced susceptibility to cecal
ligation and
puncture- and LPS-induced
sepsis, which correlated with significantly decreased survival rates and heightened levels of proinflammatory
cytokines in both peritoneal lavage and serum. Mechanistically, LPS specifically attenuated the expression of Nrp1 in macrophages, which was mediated by TLR4-NF-κB p50 and -65 pathways. By using isolated primary macrophages, loss of Nrp1 consistently resulted in increased production of proinflammatory
cytokines, including iNOS, TNF-α, and
IL-6. Together, these findings demonstrate a novel role of macrophage Nrp1 in
sepsis.-Dai, X. Okon, I., Liu, Z., Wu, Y., Zhu, H., Song, P., Zou, M.-H. A novel role for myeloid cell-specific
neuropilin 1 in mitigating
sepsis.