Myeloid-KLF2 knockout neonatal mice experience mortality from lipopolysaccharide in an age-dependent and cell-specific manner

Abstract Background: Preterm neonates exhibit increased mortality from Gram negative sepsis as compared to term neonates. The innate immune system is at a critical phase of development during the neonatal period. Mechanisms underlying activation preterm response are poorly understood. Our prior data has shown that Kruppel-like factor (KLF)-2 transcription maintain murine myeloid cells in quiescent state. We hypothesize KLF2 plays role sepsis. Methods: (P4) and (P12) knockout (MyK2KO) age matched Cre mice were given 5ug/gm E. coli O55:B5 lipopolysachharide (LPS) via intraperitoneal (i.p.) injection. For cell depletion studies, antibodies injected i.p. 24 hours LPS injection, followed by repeat dose 24h after LPS. Ly6G antibody was used for neutrophil depletion, CD115 monocyte equal both lines. Results: P4 MyK2KO have significantly within 48 h exposure (81% vs 41%, n=19, p<0.01 χ2test). At P12, there 100% survival groups mice. Depletion either neutrophils, monocytes or together, decreased 81% 55%. Conclusion: lacking an exaggerated age-matched control In vivo attenuates this response. Future studies will focus on mechanism postnatal age-specific cell-specific Supported grants Rainbow Faculty Pilot Grant (Mukherjee PI) NIH (R01 HL142647 Nayak