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Protective role of host complement system in Aspergillus fumigatus infection
Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown m...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539816/ https://www.ncbi.nlm.nih.gov/pubmed/36211424 http://dx.doi.org/10.3389/fimmu.2022.978152 |
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author | Shende, Rajashri Wong, Sarah Sze Wah Meitei, Heikrujam Thoihen Lal, Girdhari Madan, Taruna Aimanianda, Vishukumar Pal, Jayanta Kumar Sahu, Arvind |
author_facet | Shende, Rajashri Wong, Sarah Sze Wah Meitei, Heikrujam Thoihen Lal, Girdhari Madan, Taruna Aimanianda, Vishukumar Pal, Jayanta Kumar Sahu, Arvind |
author_sort | Shende, Rajashri |
collection | PubMed |
description | Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined the in vivo role of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection by Aspergillus fumigatus, the main species responsible for IA. We show that C3 knockout (C3(-/-)) mice are highly susceptible to systemic infection of A. fumigatus. Intriguingly, C4(-/-) and factor B (FB)(-/-) mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically by A. fumigatus protease. Our in vitro study substantiates the presence of C3 and C5 cleaving proteases in A. fumigatus. Examination of the importance of the terminal complement pathway employing C5(-/-) and C5aR1(-/-) mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection by A. fumigatus. |
format | Online Article Text |
id | pubmed-9539816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95398162022-10-08 Protective role of host complement system in Aspergillus fumigatus infection Shende, Rajashri Wong, Sarah Sze Wah Meitei, Heikrujam Thoihen Lal, Girdhari Madan, Taruna Aimanianda, Vishukumar Pal, Jayanta Kumar Sahu, Arvind Front Immunol Immunology Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined the in vivo role of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection by Aspergillus fumigatus, the main species responsible for IA. We show that C3 knockout (C3(-/-)) mice are highly susceptible to systemic infection of A. fumigatus. Intriguingly, C4(-/-) and factor B (FB)(-/-) mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically by A. fumigatus protease. Our in vitro study substantiates the presence of C3 and C5 cleaving proteases in A. fumigatus. Examination of the importance of the terminal complement pathway employing C5(-/-) and C5aR1(-/-) mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection by A. fumigatus. Frontiers Media S.A. 2022-09-23 /pmc/articles/PMC9539816/ /pubmed/36211424 http://dx.doi.org/10.3389/fimmu.2022.978152 Text en Copyright © 2022 Shende, Wong, Meitei, Lal, Madan, Aimanianda, Pal and Sahu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Shende, Rajashri Wong, Sarah Sze Wah Meitei, Heikrujam Thoihen Lal, Girdhari Madan, Taruna Aimanianda, Vishukumar Pal, Jayanta Kumar Sahu, Arvind Protective role of host complement system in Aspergillus fumigatus infection |
title | Protective role of host complement system in Aspergillus fumigatus infection |
title_full | Protective role of host complement system in Aspergillus fumigatus infection |
title_fullStr | Protective role of host complement system in Aspergillus fumigatus infection |
title_full_unstemmed | Protective role of host complement system in Aspergillus fumigatus infection |
title_short | Protective role of host complement system in Aspergillus fumigatus infection |
title_sort | protective role of host complement system in aspergillus fumigatus infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539816/ https://www.ncbi.nlm.nih.gov/pubmed/36211424 http://dx.doi.org/10.3389/fimmu.2022.978152 |
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