Low levels of factor H family proteins during meningococcal disease indicate systemic processes rather than specific depletion by neisseria meningitidis

Title: Low levels of factor H family proteins during meningococcal disease indicate systemic processes rather than specific depletion by neisseria meningitidis
Authors: Van Beek, AE
Pouw, RB
Wright, VJ
Sallah, N
Inwald, D
Hoggart, C
Brouwer, MC
Galassini, R
Thomas, J
Calvo-Bado, L
Fink, CG
Jongerius, I
Hibberd, M
Wouters, D
Levin, M
Kuijpers, TW
Item Type: Journal Article
Abstract: Neisseria meningitidis, the causative agent of meningococcal disease (MD), evades complement-mediated clearance upon infection by ‘hijacking’ the human complement regulator factor H (FH). The FH protein family also comprises the homologous FH-related (FHR) proteins, hypothesized to act as antagonists of FH, and FHR-3 has recently been implicated to play a major role in MD susceptibility. Here, we show that the circulating levels of all FH family proteins, not only FH and FHR-3, are equally decreased during the acute illness. We did neither observe specific consumption of FH or FHR-3 by N. meningitidis, nor of any of the other FH family proteins, suggesting that the globally reduced levels are due to systemic processes including dilution by fluid administration upon admission and vascular leakage. MD severity associated predominantly with a loss of FH rather than FHRs. Additionally, low FH levels associated with renal failure, suggesting insufficient protection of host tissue by the active protection by the FH protein family, which is reminiscent of reduced FH activity in hemolytic uremic syndrome. Retaining higher levels of FH may thus limit tissue injury during MD.
Issue Date: 26-May-2022
Date of Acceptance: 29-Apr-2022
URI: http://hdl.handle.net/10044/1/98075
DOI: 10.3389/fimmu.2022.876776
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 13
Copyright Statement: © 2022 van Beek, Pouw, Wright, Sallah, Inwald, Hoggart, Brouwer, Galassini, Thomas, Calvo-Bado, Fink, Jongerius, Hibberd, Wouters, Levin and Kuijpers. 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) and the copyright owner(s) 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.
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
complement
factor H
FHR
Neisseria meningitidis
meningococcal disease
COMPLEMENT REGULATORY DOMAINS
SUSCEPTIBILITY
ACTIVATION
BINDING
ASSOCIATION
VARIANTS
PROTECTS
RISK
FHR
Neisseria meningitidis
complement
factor H
meningococcal disease
Complement Factor H
Complement System Proteins
Hemolytic-Uremic Syndrome
Humans
Meningococcal Infections
Neisseria meningitidis
Humans
Neisseria meningitidis
Meningococcal Infections
Hemolytic-Uremic Syndrome
Complement Factor H
Complement System Proteins
Science & Technology
Life Sciences & Biomedicine
Immunology
complement
factor H
FHR
Neisseria meningitidis
meningococcal disease
COMPLEMENT REGULATORY DOMAINS
SUSCEPTIBILITY
ACTIVATION
BINDING
ASSOCIATION
VARIANTS
PROTECTS
RISK
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN 876776
Appears in Collections:Department of Infectious Diseases



This item is licensed under a Creative Commons License Creative Commons