Inhibition of the Classical Pathway of Complement Activation Impairs Bacterial Clearance during Enterococcus faecalis Infection
infections are considered a major public health concern worldwide. The complement system has a crucial role in the protection against different microbial pathogens, including Complement can be activated through three different pathways, including the classical, lectin, and alternative pathways. Ther...
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Published in | Infection and immunity Vol. 89; no. 5 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
16.04.2021
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Subjects | |
Online Access | Get full text |
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Summary: | infections are considered a major public health concern worldwide. The complement system has a crucial role in the protection against different microbial pathogens, including
Complement can be activated through three different pathways, including the classical, lectin, and alternative pathways. There is limited information on the role of the classical pathway (CP) in protection against infections caused by
In the present study, we generated Fab fragments that successfully block the CP in mouse via inhibition of a key enzyme, C1s-A. Our results showed that anti-C1s-A Fab fragments block CP-mediated C3b and C4b deposition
We further showed that administration of anti-C1s-A Fab fragments significantly impairs the CP functional activity
Moreover, treatment of mice infected with
using anti-C1s-A Fab fragments significantly impairs bacterial clearance as determined from the viable bacterial counts recovered from blood, kidneys, spleens, livers, and lungs of infected mice. Overall, this study highlights the essential role of the CP in host defense against
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Ramadan Hassan and Youssif M. Ali contributed equally to this article. Citation Shehab El-Din EMR, Elgaml A, Ali YM, Hassan R. 2021. Inhibition of the classical pathway of complement activation impairs bacterial clearance during Enterococcus faecalis infection. Infect Immun 89:e00660-20. https://doi.org/10.1128/IAI.00660-20. |
ISSN: | 0019-9567 1098-5522 |
DOI: | 10.1128/IAI.00660-20 |