Early Terminal Complement Blockade and C6 Deficiency Are Protective in Enterohemorrhagic Escherichia coli-Infected Mice.

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 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.

• Authors: Ida Arvidsson, Johan Rebetz, Sebastian Loos, Maria Herthelius, Ann-Charlotte Kristoffersson, Elisabet Englund, Milan Chromek, Diana Karpman
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 197 Issue 4 Pg. 1276-86 (08 15 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 27421478 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Complement C6
• Complement Membrane Attack Complex

Topics

• Animals
• Child, Preschool
• Complement C6 (antagonists & inhibitors, immunology)
• Complement Membrane Attack Complex (antagonists & inhibitors, immunology)
• Disease Models, Animal
• Enterohemorrhagic Escherichia coli
• Escherichia coli Infections (immunology)
• Female
• Hemolytic-Uremic Syndrome (immunology)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL