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Early terminal complement blockade and C6 deficiency are protective in enterohemorrhagic Escherichia coli-infected mice

Arvidsson, Ida LU ; Rebetz, Johan LU ; Loos, Sebastian LU ; Herthelius, Maria; Kristoffersson, Ann Charlotte LU ; Englund, Elisabet LU ; Chromek, Milan LU and Karpman, Diana LU (2016) In Journal of Immunology 197(4). p.1276-1286
Abstract

Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with... (More)

Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with anti-C5 on day 3 developed symptoms (three of eight, p < 0.01 compared with mice treated with the irrelevant Ab on day 3) whereas most mice treated with anti-C5 on day 6 developed symptoms (six of eight). C6-deficient C57BL/6 mice were also inoculated with E. coli O157:H7 and only 1 of 14 developed disease, whereas 10 of 16 wild-type mice developed weight loss and severe disease (p < 0.01). Complement activation via the terminal pathway is thus involved in the development of disease in murine EHEC infection. Early blockade of the terminal complement pathway, before the development of symptoms, was largely protective, whereas late blockade was not. Likewise, lack of C6, and thereby deficient terminal complement complex, was protective in murine E. coli O157:H7 infection.

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publication status
published
subject
keywords
enterohemorrhagic, mice, C6 deficiency
in
Journal of Immunology
volume
197
issue
4
pages
11 pages
publisher
American Association of Immunologists
external identifiers
  • Scopus:84983799701
  • WOS:000384999100027
ISSN
0022-1767
DOI
10.4049/jimmunol.1502377
language
English
LU publication?
yes
id
bfc78cf8-0836-4195-a601-53a4db41e239
date added to LUP
2016-09-21 22:47:23
date last changed
2017-02-05 04:53:10
@article{bfc78cf8-0836-4195-a601-53a4db41e239,
  abstract     = {<p>Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with anti-C5 on day 3 developed symptoms (three of eight, p &lt; 0.01 compared with mice treated with the irrelevant Ab on day 3) whereas most mice treated with anti-C5 on day 6 developed symptoms (six of eight). C6-deficient C57BL/6 mice were also inoculated with E. coli O157:H7 and only 1 of 14 developed disease, whereas 10 of 16 wild-type mice developed weight loss and severe disease (p &lt; 0.01). Complement activation via the terminal pathway is thus involved in the development of disease in murine EHEC infection. Early blockade of the terminal complement pathway, before the development of symptoms, was largely protective, whereas late blockade was not. Likewise, lack of C6, and thereby deficient terminal complement complex, was protective in murine E. coli O157:H7 infection.</p>},
  author       = {Arvidsson, Ida and Rebetz, Johan and Loos, Sebastian and Herthelius, Maria and Kristoffersson, Ann Charlotte and Englund, Elisabet and Chromek, Milan and Karpman, Diana},
  issn         = {0022-1767},
  keyword      = {enterohemorrhagic,mice,C6 deficiency },
  language     = {eng},
  month        = {08},
  number       = {4},
  pages        = {1276--1286},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Early terminal complement blockade and C6 deficiency are protective in enterohemorrhagic Escherichia coli-infected mice},
  url          = {http://dx.doi.org/10.4049/jimmunol.1502377},
  volume       = {197},
  year         = {2016},
}