Aspf2 From Aspergillus fumigatus Recruits Human Immune Regulators for Immune Evasion and Cell Damage

Frontiers in Immunology
Prasad DasariPeter F Zipfel

Abstract

The opportunistic fungal pathogen Aspergillus fumigatus can cause life-threatening infections, particularly in immunocompromised patients. Most pathogenic microbes control host innate immune responses at the earliest time, already before infiltrating host immune cells arrive at the site of infection. Here, we identify Aspf2 as the first A. fumigatus Factor H-binding protein. Aspf2 recruits several human plasma regulators, Factor H, factor-H-like protein 1 (FHL-1), FHR1, and plasminogen. Factor H contacts Aspf2 via two regions located in SCRs6-7 and SCR20. FHL-1 binds via SCRs6-7, and FHR1 via SCRs3-5. Factor H and FHL-1 attached to Aspf2-maintained cofactor activity and assisted in C3b inactivation. A Δaspf2 knockout strain was generated which bound Factor H with 28% and FHL-1 with 42% lower intensity. In agreement with less immune regulator acquisition, when challenged with complement-active normal human serum, Δaspf2 conidia had substantially more C3b (>57%) deposited on their surface. Consequently, Δaspf2 conidia were more efficiently phagocytosed (>20%) and killed (44%) by human neutrophils as wild-type conidia. Furthermore, Aspf2 recruited human plasminogen and, when activated by tissue-type plasminogen activator, newly ge...Continue Reading

References

Nov 1, 1989·Infection and Immunity·T R KozelS M Levitz
May 19, 2000·Methods : a Companion to Methods in Enzymology·K LähteenmäkiT K Korhonen
Apr 12, 2001·The New England Journal of Medicine·M J Walport
Nov 30, 2006·The Journal of Biological Chemistry·Mukesh PasupuletiArtur Schmidtchen
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sven HammerschmidtPeter F Zipfel
Sep 26, 2007·Advances in Experimental Medicine and Biology·Peter F ZipfelChristine Skerka
Sep 26, 2007·Advances in Experimental Medicine and Biology·Martin Malmsten, Artur Schmidtchen
Oct 26, 2007·The Journal of Biological Chemistry·Sophia PoltermannPeter F Zipfel
Nov 28, 2007·Infection and Immunity·Judith BehnsenPeter F Zipfel
Jun 21, 2008·PLoS Genetics·Aimee K ZaasDavid A Schwartz
Jul 15, 2009·Clinical Microbiology Reviews·Taylor R T Dagenais, Nancy P Keller
Jul 28, 2009·The Journal of Biological Chemistry·Ying Jie MaPeter Garred
Sep 5, 2009·Nature Reviews. Immunology·Peter F Zipfel, Christine Skerka
May 26, 2010·Infection and Immunity·Judith BehnsenAxel A Brakhage
Apr 1, 2008·Proteomics. Clinical Applications·Jinzhi ChenLynn M Schnapp
May 14, 2011·International Journal of Medical Microbiology : IJMM·Peter F ZipfelShanshan Luo
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Anil K GhoshMarcelo Jacobs-Lorena
Mar 28, 2012·The Journal of Biological Chemistry·Diana BarthelPeter F Zipfel
Jul 5, 2012·PLoS Pathogens·Francesco CitiuloDuncan Wilson
Jul 27, 2012·Cell Reports·Ruby H P LawJames C Whisstock
Aug 29, 2012·Interdisciplinary Perspectives on Infectious Diseases·Cornelia Speth, Günter Rambach
Oct 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Teresia HallströmPeter F Zipfel
May 3, 2013·PLoS Pathogens·T MeriT S Jokiranta
May 28, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer A BartlettKatherine E Williams
Jul 3, 2013·Molecular Immunology·Peter F ZipfelKristian Riesbeck
Jul 9, 2013·Molecular Immunology·Christine SkerkaLubka T Roumenina
Nov 19, 2014·Seminars in Immunopathology·Thorsten HeinekampAxel A Brakhage

❮ Previous
Next ❯

Citations

Jan 30, 2020·FEBS Letters·Raffaella ParenteAntonio Inforzato
Oct 6, 2020·Frontiers in Immunology·Alexander TilleMarc Thilo Figge
Sep 27, 2020·Cellular Microbiology·Annika KönigBernhard Hube
Oct 31, 2020·Frontiers in Microbiology·Esther M KeizerHans de Cock
Jul 16, 2019·Current Opinion in Immunology·Lee-Ann H Allen, Alison K Criss
Feb 2, 2021·FEMS Microbiology Reviews·Antonia LastBernhard Hube
Mar 16, 2021·Frontiers in Immunology·Sara R MooreViviana P Ferreira

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
biolayer interferometry
biosensor
Assay
FCS
flow cytometry
scanning electron microscopy
ELISA
enzyme-linked immunosorbent assay
Knockout

Software Mentioned

Flowjo
SciPy
BLITZ
NumPy
ZEN
Graphpad5
GraphPad
openCV
CEWA
Graphpad Prism

Related Concepts

Related Feeds

Aspergillosis

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Aspergillosis (ASM)

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Anja KunertPeter F Zipfel
The Journal of Immunology : Official Journal of the American Association of Immunologists
Diana BarthelPeter F Zipfel
© 2022 Meta ULC. All rights reserved