Lactoferrin Supplementation Improves Neonatal Phagocyte Function in a Murine Model of E. coli Sepsis 2261096

Abstract

Abstract Introduction E.coli K1 is a neonatal specific pathogen with extremely high mortality rates. We hypothesize this mortality is a result of the decreased phagocytic capacity of neonatal immune cells in combination with decreased barrier function due to their open gut barrier. Lactoferrin(LF) is an immune modulator present in all breastmilk. Importantly, it has also been shown to increase support intestinal barrier function. . Utilizing our murine model, we seek to determine the efficacy of LF supplementation on influencing sepsis-associated outcomes. Methods Neonates were enterally gavaged with 0.3mg/g body weight LF or PBS control daily from P0 to P4/5. Sepsis was induced by oral gavage or IP injection of E.coli K1 on P4/5. Results LF significantly decreased sepsis-associated morbidity(p < 0.0001) and mortality(p<.01). LF decreased intestinal permeability (p < 0.0001) and subsequent E.coli translocation into the IP cavity(p=.0011), bacteremia severity was equivalent in both groups (p = 0.3). Serum cytokines were also equivalent in both groups. However, significant difference in immune responses were seen. 12 hours post infection(hpi), LF pups have a higher macrophage (p<.001) count in the IP cavity than control pups, with a higher frequency of activated macrophages(p<.01). 12hpi, LF pups trend towards an increased neutrophil count in the IP cavity(p=.06) and have a significant increase in the frequency of activated neutrophils(p=.05). At 18 hpi, LF and control pups have broadly equivalent frequencies of activated neutrophils, but LF pups have a higher proportion of TLR2+ neutrophils (p=.05) within their activated population. Further immune phenotyping of the IP cavity and spleen/systemic response are underway. Conclusion LF increases phagocyte activation without a cytokine storm, tempering morbidity and ultimately decreasing mortality following E.coli K1 sepsis. Funding Source 1R01AI150687-01 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)