Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1457174

Host Heterogeneity in Humoral Bactericidal Activity Can be Complement Independent

Provisionally accepted
Ryuichiro Abe Ryuichiro Abe 1,2Nikhil Ram Mohan Nikhil Ram Mohan 1Elizabeth J. Zudock Elizabeth J. Zudock 1Shawna Lewis Shawna Lewis 3Karen C. Carroll Karen C. Carroll 3Samuel Yang Samuel Yang 1*
  • 1 Stanford University, Stanford, California, United States
  • 2 Osaka University, Suita, Japan
  • 3 Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States

The final, formatted version of the article will be published soon.

    Humoral bactericidal activity was first recognized nearly a century ago. However, the extent of interindividual heterogeneity and the mechanisms underlying such heterogeneity beyond antibody or complement systems have not been well studied. We analyzed the plasma bactericidal activity of five healthy volunteers against 30 strains of Gram-negative uropathogens, Klebsiella pneumoniae and Escherichia coli, associated with bloodstream infections. We revealed wide variations in plasma bactericidal activities 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 inhibitor assays elucidated that the complement-mediated killing was not responsible for the inter-individual heterogeneity in either isolate. Furthermore, using MALDI-TOF mass spectrometry on plasmas of 25 healthy individuals, we screened for plasma metabolome components causing the interindividual heterogeneity and identified several small molecules including gangliosides, pediocins, or saponins as candidates. 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.

    Keywords: humoral bactericidal activity, serum antibacterial activity, inter-individual heterogeneity, diagnosis of bacterial infection, Bloodstream infection, humoral innate immunity, Sepsis endotyping, trained immunity

    Received: 30 Jun 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Abe, Ram Mohan, Zudock, Lewis, Carroll and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Samuel Yang, Stanford University, Stanford, 94305, California, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.