Haemophilus influenzae interacts with the human complement inhibitor factor H
Hallström, Teresia LU ; Zipfel, Peter F. ; Blom, Anna LU
; Lauer, Nadine
; Forsgren, Arne
LU
and Riesbeck, Kristian
LU
(2008)
In Journal of Immunology
181(1).
p.537-545
- Abstract
- Pathogenic microbes acquire human complement inhibitors to circumvent the innate immune system. In this study, we identify two novel host-pathogen interactions, factor H (FH) and factor H-like protein 1 (FHL-1), the inhibitors of the alternative pathway that binds to Hib. A collection of clinical Haemophilus influenzae isolates was tested and the majority of encapsulated and unencapsulated bound FH. The isolate Hib 541 with a particularly high FH-binding was selected for detailed analysis. An increased survival in normal human serum was observed with Hib 541 as compared with the low FH-binding Hib 568. Interestingly, two binding domains were identified within FH; one binding site common to both FH and FHL-1 was located in the N-terminal... (More)
- Pathogenic microbes acquire human complement inhibitors to circumvent the innate immune system. In this study, we identify two novel host-pathogen interactions, factor H (FH) and factor H-like protein 1 (FHL-1), the inhibitors of the alternative pathway that binds to Hib. A collection of clinical Haemophilus influenzae isolates was tested and the majority of encapsulated and unencapsulated bound FH. The isolate Hib 541 with a particularly high FH-binding was selected for detailed analysis. An increased survival in normal human serum was observed with Hib 541 as compared with the low FH-binding Hib 568. Interestingly, two binding domains were identified within FH; one binding site common to both FH and FHL-1 was located in the N-terminal short consensus repeat domains 6-7, whereas the other, specific for FH, was located in the C-terminal short consensus repeat domains 18-20. Importantly, both FH and FHL-1, when bound to the surface of Hib 541, retained cofactor activity as determined by analysis of C3b degradation. Two H. influenzae outer membrane proteins of similar to 32 and 40 kDa were detected with radiolabeled FH in Far Western blot. Taken together, in addition to interactions with the classical, lectin, and terminal pathways, H. influenzae interferes with the alternative complement activation pathway by binding FH and FHL-1, and thereby reducing the complement-mediated bactericidal activity resulting in an increased survival. In contrast to incubation with active complement, H. influenzae had a reduced survival in FH-depleted human serum, thus demonstrating that FH mediates a protective role at the bacterial surface. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1257005
- author
- Hallström, Teresia
LU
; Zipfel, Peter F.
; Blom, Anna
LU
; Lauer, Nadine
; Forsgren, Arne
LU
and Riesbeck, Kristian
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 181
- issue
- 1
- pages
- 537 - 545
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000257404900060
- scopus:47949122480
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- id
- b9fbcd23-7351-400b-aee4-6c6a0d905491 (old id 1257005)
- alternative location
- http://www.jimmunol.org/cgi/content/abstract/181/1/537
- date added to LUP
- 2016-04-01 13:21:43
- date last changed
- 2022-05-15 04:45:19
@article{b9fbcd23-7351-400b-aee4-6c6a0d905491,
abstract = {{Pathogenic microbes acquire human complement inhibitors to circumvent the innate immune system. In this study, we identify two novel host-pathogen interactions, factor H (FH) and factor H-like protein 1 (FHL-1), the inhibitors of the alternative pathway that binds to Hib. A collection of clinical Haemophilus influenzae isolates was tested and the majority of encapsulated and unencapsulated bound FH. The isolate Hib 541 with a particularly high FH-binding was selected for detailed analysis. An increased survival in normal human serum was observed with Hib 541 as compared with the low FH-binding Hib 568. Interestingly, two binding domains were identified within FH; one binding site common to both FH and FHL-1 was located in the N-terminal short consensus repeat domains 6-7, whereas the other, specific for FH, was located in the C-terminal short consensus repeat domains 18-20. Importantly, both FH and FHL-1, when bound to the surface of Hib 541, retained cofactor activity as determined by analysis of C3b degradation. Two H. influenzae outer membrane proteins of similar to 32 and 40 kDa were detected with radiolabeled FH in Far Western blot. Taken together, in addition to interactions with the classical, lectin, and terminal pathways, H. influenzae interferes with the alternative complement activation pathway by binding FH and FHL-1, and thereby reducing the complement-mediated bactericidal activity resulting in an increased survival. In contrast to incubation with active complement, H. influenzae had a reduced survival in FH-depleted human serum, thus demonstrating that FH mediates a protective role at the bacterial surface.}},
author = {{Hallström, Teresia and Zipfel, Peter F. and Blom, Anna and Lauer, Nadine and Forsgren, Arne and Riesbeck, Kristian}},
issn = {{1550-6606}},
language = {{eng}},
number = {{1}},
pages = {{537--545}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Haemophilus influenzae interacts with the human complement inhibitor factor H}},
url = {{http://www.jimmunol.org/cgi/content/abstract/181/1/537}},
volume = {{181}},
year = {{2008}},
}