Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae.
The complement-like pathway of the African malaria mosquito Anopheles gambiae provides protection against infection by diverse pathogens. A functional requirement for a core set of proteins during infections by rodent and human malaria parasites, bacteria, and fungi suggests a similar mechanism oper...
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Online Access: | https://doi.org/10.1371/journal.pone.0214753 |
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doaj-ffbdbd3bb1f5471bb79ed96f8dfcd77e2021-03-03T20:45:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021475310.1371/journal.pone.0214753Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae.Valeria M Reyes RuizGregory L SousaSarah D SneedKatie V FarrantGeorge K ChristophidesMichael PovelonesThe complement-like pathway of the African malaria mosquito Anopheles gambiae provides protection against infection by diverse pathogens. A functional requirement for a core set of proteins during infections by rodent and human malaria parasites, bacteria, and fungi suggests a similar mechanism operates against different pathogens. However, the extent to which the molecular mechanisms are conserved is unknown. In this study we probed the biochemical responses of complement-like pathway to challenge by the Gram-positive bacterium Staphyloccocus aureus. Western blot analysis of the hemolymph revealed that S. aureus challenge activates a TEP1 convertase-like activity and promotes the depletion of the protein SPCLIP1. S. aureus challenge did not lead to an apparent change in the abundance of the LRIM1/APL1C complex compared to challenge by the Gram-negative bacterium, Escherichia coli. Following up on this observation using a panel of LRIM1 and APL1C antibodies, we found that E. coli challenge, but not S. aureus, specifically activates a protease that cleaves the C-terminus of APL1C. Inhibitor studies in vivo and in vitro protease assays suggest that a serine protease is responsible for APL1C cleavage. This study reveals that despite different challenges converging on activation of a TEP1 convertase-like activity, the mosquito complement-like pathway also includes pathogen-specific reactions.https://doi.org/10.1371/journal.pone.0214753 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valeria M Reyes Ruiz Gregory L Sousa Sarah D Sneed Katie V Farrant George K Christophides Michael Povelones |
spellingShingle |
Valeria M Reyes Ruiz Gregory L Sousa Sarah D Sneed Katie V Farrant George K Christophides Michael Povelones Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae. PLoS ONE |
author_facet |
Valeria M Reyes Ruiz Gregory L Sousa Sarah D Sneed Katie V Farrant George K Christophides Michael Povelones |
author_sort |
Valeria M Reyes Ruiz |
title |
Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae. |
title_short |
Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae. |
title_full |
Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae. |
title_fullStr |
Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae. |
title_full_unstemmed |
Stimulation of a protease targeting the LRIM1/APL1C complex reveals specificity in complement-like pathway activation in Anopheles gambiae. |
title_sort |
stimulation of a protease targeting the lrim1/apl1c complex reveals specificity in complement-like pathway activation in anopheles gambiae. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
The complement-like pathway of the African malaria mosquito Anopheles gambiae provides protection against infection by diverse pathogens. A functional requirement for a core set of proteins during infections by rodent and human malaria parasites, bacteria, and fungi suggests a similar mechanism operates against different pathogens. However, the extent to which the molecular mechanisms are conserved is unknown. In this study we probed the biochemical responses of complement-like pathway to challenge by the Gram-positive bacterium Staphyloccocus aureus. Western blot analysis of the hemolymph revealed that S. aureus challenge activates a TEP1 convertase-like activity and promotes the depletion of the protein SPCLIP1. S. aureus challenge did not lead to an apparent change in the abundance of the LRIM1/APL1C complex compared to challenge by the Gram-negative bacterium, Escherichia coli. Following up on this observation using a panel of LRIM1 and APL1C antibodies, we found that E. coli challenge, but not S. aureus, specifically activates a protease that cleaves the C-terminus of APL1C. Inhibitor studies in vivo and in vitro protease assays suggest that a serine protease is responsible for APL1C cleavage. This study reveals that despite different challenges converging on activation of a TEP1 convertase-like activity, the mosquito complement-like pathway also includes pathogen-specific reactions. |
url |
https://doi.org/10.1371/journal.pone.0214753 |
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