The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut

Rhodnius prolixus is an insect vector of Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Nuclear factor-κB (NF-κB) transcription factors (TF) are conserved components of the innate immune system in several multicellular organisms including insects. The drug IMD-0354 [N-(3,...

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Main Authors:	Cecilia S. Vieira, Otacílio C. Moreira, Kate K. S. Batista, Norman A. Ratcliffe, Daniele P. Castro, Patrícia Azambuja
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2018-08-01
Series:	Frontiers in Physiology
Subjects:	insect immune system Rhodnius prolixus antimicrobial peptides Nf-κB transcription factor Trypanosoma cruzi microbiota
Online Access:	https://www.frontiersin.org/article/10.3389/fphys.2018.01189/full

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spelling	doaj-art-9a5957c7e486451bb65194124bfed6cd2018-08-31T14:19:47ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-08-01910.3389/fphys.2018.01189383334The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus MidgutCecilia S. Vieira0Otacílio C. Moreira1Kate K. S. Batista2Norman A. Ratcliffe3Norman A. Ratcliffe4Daniele P. Castro5Daniele P. Castro6Patrícia Azambuja7Patrícia Azambuja8Laboratório de Bioquímica e Fisiologia de Insetos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Bioquímica e Fisiologia de Insetos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Biologia de Insetos, Universidade Federal Fluminense, Niterói, BrazilCollege of Science, Swansea University, Wales, United KingdomLaboratório de Bioquímica e Fisiologia de Insetos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, BrazilDepartamento de Entomologia Molecular, Instituto Nacional de Entomologia Molecular (INCT-EM), Rio de Janeiro, BrazilLaboratório de Bioquímica e Fisiologia de Insetos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, BrazilDepartamento de Entomologia Molecular, Instituto Nacional de Entomologia Molecular (INCT-EM), Rio de Janeiro, BrazilRhodnius prolixus is an insect vector of Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Nuclear factor-κB (NF-κB) transcription factors (TF) are conserved components of the innate immune system in several multicellular organisms including insects. The drug IMD-0354 [N-(3,5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] is a selective inhibitor of IκB kinases. It blocks IκBα phosphorylation thus preventing nuclear translocation of the NF-κb TF. In humans, NF-κB is involved in several biological processes such as inflammation, cell proliferation and immunity. In insects, the activation of the immune system upon microbial challenge can be controlled by signaling pathways such as the immune deficiency (IMD) and Toll, to combat infection. These activated pathways signal to downstream NF-κB TF to stimulate specific immune genes, triggering the synthesis of several molecules such as the antimicrobial peptides. In Drosophila melanogaster, the activation and regulation of NF-κB TF have been elucidated, while in triatomines these mechanisms are not fully understood Therefore, the present study investigated the effects of oral administration of the drug IMD-0354 on the R. prolixus immune response to challenge with bacteria and T. cruzi, as well as the impact on the gut bacterial microbiota. R. prolixus were fed with rabbit blood containing IMD-0354 and Escherichia coli, Staphylococcus aureus, or T. cruzi. The effects of IMD-0354 on insect mortality and antimicrobial activity in insect midgut samples, as well as the relative expression of R. prolixus immune genes were recorded. The bacterial microbiota was analyzed, and viable parasites were counted in insect midgut samples. The IMD-0354 treatment modulated antibacterial activity and the gene expression patterns of defensin A, defensin B, defensin C, and prolixicin, and the genes involved in the IMD and Toll pathways. Additionally, there was an increase of bacterial microbiota in treated insects. Insects treated with IMD-0354 and concomitantly infected with bacteria or T. cruzi through the blood meal had increased mortality, while the T. cruzi population in R. prolixus midgut was reduced. The inhibitory effect of IMD-0354 indicates the importance of NF-κB TF in the innate immune responses involved in the control of bacteria and parasite infections in the R. prolixus midgut.https://www.frontiersin.org/article/10.3389/fphys.2018.01189/fullinsect immune systemRhodnius prolixusantimicrobial peptidesNf-κB transcription factorTrypanosoma cruzimicrobiota
institution	Open Data Bank
collection	Open Access Journals
building	Directory of Open Access Journals
language	English
format	Article
author	Cecilia S. Vieira Otacílio C. Moreira Kate K. S. Batista Norman A. Ratcliffe Norman A. Ratcliffe Daniele P. Castro Daniele P. Castro Patrícia Azambuja Patrícia Azambuja
spellingShingle	Cecilia S. Vieira Otacílio C. Moreira Kate K. S. Batista Norman A. Ratcliffe Norman A. Ratcliffe Daniele P. Castro Daniele P. Castro Patrícia Azambuja Patrícia Azambuja The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut Frontiers in Physiology insect immune system Rhodnius prolixus antimicrobial peptides Nf-κB transcription factor Trypanosoma cruzi microbiota
author_facet	Cecilia S. Vieira Otacílio C. Moreira Kate K. S. Batista Norman A. Ratcliffe Norman A. Ratcliffe Daniele P. Castro Daniele P. Castro Patrícia Azambuja Patrícia Azambuja
author_sort	Cecilia S. Vieira
title	The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut
title_short	The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut
title_full	The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut
title_fullStr	The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut
title_full_unstemmed	The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut
title_sort	nf-κb inhibitor, imd-0354, affects immune gene expression, bacterial microbiota and trypanosoma cruzi infection in rhodnius prolixus midgut
publisher	Frontiers Media S.A.
series	Frontiers in Physiology
issn	1664-042X
publishDate	2018-08-01
description	Rhodnius prolixus is an insect vector of Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Nuclear factor-κB (NF-κB) transcription factors (TF) are conserved components of the innate immune system in several multicellular organisms including insects. The drug IMD-0354 [N-(3,5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] is a selective inhibitor of IκB kinases. It blocks IκBα phosphorylation thus preventing nuclear translocation of the NF-κb TF. In humans, NF-κB is involved in several biological processes such as inflammation, cell proliferation and immunity. In insects, the activation of the immune system upon microbial challenge can be controlled by signaling pathways such as the immune deficiency (IMD) and Toll, to combat infection. These activated pathways signal to downstream NF-κB TF to stimulate specific immune genes, triggering the synthesis of several molecules such as the antimicrobial peptides. In Drosophila melanogaster, the activation and regulation of NF-κB TF have been elucidated, while in triatomines these mechanisms are not fully understood Therefore, the present study investigated the effects of oral administration of the drug IMD-0354 on the R. prolixus immune response to challenge with bacteria and T. cruzi, as well as the impact on the gut bacterial microbiota. R. prolixus were fed with rabbit blood containing IMD-0354 and Escherichia coli, Staphylococcus aureus, or T. cruzi. The effects of IMD-0354 on insect mortality and antimicrobial activity in insect midgut samples, as well as the relative expression of R. prolixus immune genes were recorded. The bacterial microbiota was analyzed, and viable parasites were counted in insect midgut samples. The IMD-0354 treatment modulated antibacterial activity and the gene expression patterns of defensin A, defensin B, defensin C, and prolixicin, and the genes involved in the IMD and Toll pathways. Additionally, there was an increase of bacterial microbiota in treated insects. Insects treated with IMD-0354 and concomitantly infected with bacteria or T. cruzi through the blood meal had increased mortality, while the T. cruzi population in R. prolixus midgut was reduced. The inhibitory effect of IMD-0354 indicates the importance of NF-κB TF in the innate immune responses involved in the control of bacteria and parasite infections in the R. prolixus midgut.
topic	insect immune system Rhodnius prolixus antimicrobial peptides Nf-κB transcription factor Trypanosoma cruzi microbiota
url	https://www.frontiersin.org/article/10.3389/fphys.2018.01189/full
_version_	1612661749051293696

The NF-κB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut

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