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Examining the role of macrolides and host immunity in combatting filarial parasites
Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability t...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391593/ https://www.ncbi.nlm.nih.gov/pubmed/28410595 http://dx.doi.org/10.1186/s13071-017-2116-6 |
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author | Carithers, Doug S. |
author_facet | Carithers, Doug S. |
author_sort | Carithers, Doug S. |
collection | PubMed |
description | Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also thought to be the ML mode of action against filarial nematodes, but researchers have not been able to validate these characteristic effects of immobilization/starvation of MLs in vitro, even at higher doses than are possible in vivo. Relatively recently, ML receptor sites exclusively located proximate to the excretory-secretory (ES) apparatus were identified in Brugia malayi microfilaria and an ML-induced suppression of secretory protein release by B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that suppression of these ES proteins prevents the filarial worm from interfering with the host’s complement cascade, reducing the ability of the parasite to evade the immune system. Live microfilariae and/or larvae, thus exposed, are attacked and presented to the host’s innate immune mechanisms and are ultimately killed by the immune response, not the ML drug. These live, exposed filarial worms stimulate development of innate, cellular and humoral immune responses that when properly stimulated, are capable of clearing all larvae or microfilariae present in the host, regardless of their individual sensitivity to MLs. Additional research in this area can be expected to improve our understanding of the relationships among filarial worms, MLs, and the host immune system, which likely would have implications in filarial disease management in humans and animals. |
format | Online Article Text |
id | pubmed-5391593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53915932017-04-17 Examining the role of macrolides and host immunity in combatting filarial parasites Carithers, Doug S. Parasit Vectors Review Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also thought to be the ML mode of action against filarial nematodes, but researchers have not been able to validate these characteristic effects of immobilization/starvation of MLs in vitro, even at higher doses than are possible in vivo. Relatively recently, ML receptor sites exclusively located proximate to the excretory-secretory (ES) apparatus were identified in Brugia malayi microfilaria and an ML-induced suppression of secretory protein release by B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that suppression of these ES proteins prevents the filarial worm from interfering with the host’s complement cascade, reducing the ability of the parasite to evade the immune system. Live microfilariae and/or larvae, thus exposed, are attacked and presented to the host’s innate immune mechanisms and are ultimately killed by the immune response, not the ML drug. These live, exposed filarial worms stimulate development of innate, cellular and humoral immune responses that when properly stimulated, are capable of clearing all larvae or microfilariae present in the host, regardless of their individual sensitivity to MLs. Additional research in this area can be expected to improve our understanding of the relationships among filarial worms, MLs, and the host immune system, which likely would have implications in filarial disease management in humans and animals. BioMed Central 2017-04-14 /pmc/articles/PMC5391593/ /pubmed/28410595 http://dx.doi.org/10.1186/s13071-017-2116-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Carithers, Doug S. Examining the role of macrolides and host immunity in combatting filarial parasites |
title | Examining the role of macrolides and host immunity in combatting filarial parasites |
title_full | Examining the role of macrolides and host immunity in combatting filarial parasites |
title_fullStr | Examining the role of macrolides and host immunity in combatting filarial parasites |
title_full_unstemmed | Examining the role of macrolides and host immunity in combatting filarial parasites |
title_short | Examining the role of macrolides and host immunity in combatting filarial parasites |
title_sort | examining the role of macrolides and host immunity in combatting filarial parasites |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391593/ https://www.ncbi.nlm.nih.gov/pubmed/28410595 http://dx.doi.org/10.1186/s13071-017-2116-6 |
work_keys_str_mv | AT carithersdougs examiningtheroleofmacrolidesandhostimmunityincombattingfilarialparasites |