Immunoactivating Peptide P4 Augments Alveolar Macrophage Phagocytosis in Two Diverse Human Populations |
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| Authors: | Mathieu Bangert Adam K. Wright Jamie Rylance Matthew J. Kelly Angela D. Wright George M. Carlone Jacquelyn S. Sampson Gowrisankar Rajam Edwin W. Ades Aras Kadioglu Stephen B. Gordon |
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| Affiliation: | Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdoma;Malawi-Liverpool-Wellcome Clinical Research Laboratories, Blantyre, Malawib;Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USAc;Clinical Infection, Microbiology and Immunology, Institute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdomd |
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| Abstract: | New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniaeex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells. |
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