Host heterogeneity in humoral bactericidal activity can be complement independent.

Autor:	Abe R; Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, CA, United States.; Laboratory of Bacterial Pathogenesis, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan., Ram-Mohan N; Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, CA, United States., Zudock EJ; Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, CA, United States., Lewis S; Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Carroll KC; Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Yang S; Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Sep 18; Vol. 15, pp. 1457174. Date of Electronic Publication: 2024 Sep 18 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1457174
Abstrakt:	Background: Humoral bactericidal activity was first recognized nearly a century ago. However, the extent of inter-individual heterogeneity and the mechanisms underlying such heterogeneity beyond antibody or complement systems have not been well studied. Methods: The plasma bactericidal activity of five healthy volunteers were tested against 30 strains of Gram-negative uropathogens, Klebsiella pneumoniae and Escherichia coli, associated with bloodstream infections. IgG and IgM titers specific to K. pneumoniae strains KP13883 and KPB1 were measured by ELISA, and complement inhibitor was used to measure the contribution of complement-induced killing. Furthermore, MALDI-TOF mass spectrometry was conducted to determine the metabolomic components of plasma with bactericidal properties in 25 healthy individuals using Bayesian inference of Pearson correlation between peak intensity and colony counts of surviving bacteria. Results: Plasma bactericidal activity varied widely between individuals against various bacterial strains. While individual plasma with higher IgM titers specific to K. pneumoniae strain KP13883 showed more efficient killing of the strain, both IgM and IgG titers for K. pneumoniae strain KPB1 did not correlate well with the killing activity. Complement inhibition assays elucidated that the complement-mediated killing was not responsible for the inter-individual heterogeneity in either isolate. Subsequently, using MALDI-TOF mass spectrometry on plasmas of 25 healthy individuals, we identified several small molecules including gangliosides, pediocins, or saponins as candidates that showed negative correlation between peak intensities and colony forming units of the test bacteria. Conclusion: This is the first study to demonstrate the inter-individual heterogeneity of constitutive innate humoral bactericidal function quantitatively and that the heterogeneity can be independent of antibody or the complement system. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Abe, Ram-Mohan, Zudock, Lewis, Carroll and Yang.)
Databáze:	MEDLINE
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