MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses

Recent studies have provided emerging evidence of the critical involvement of microRNAs in host immune defence against bacterial infection and that likewise the expression of the miRNAs is profoundly impacted by a variety of pathogens to subvert the immune response. Here, we report the role of hsa-l...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Agnieszka Magryś, Agnieszka Bogut
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Staphylococcus epidermidis Small Colony Variants MicroRNA Hsa-let-7a Macrophages Microbiology QR1-502 Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/ce72f8ec134642da8899381526efc13c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ce72f8ec134642da8899381526efc13c
record_format	dspace
spelling	oai:doaj.org-article:ce72f8ec134642da8899381526efc13c2021-12-02T04:59:58ZMicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses1438-422110.1016/j.ijmm.2021.151542https://doaj.org/article/ce72f8ec134642da8899381526efc13c2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1438422121000710https://doaj.org/toc/1438-4221Recent studies have provided emerging evidence of the critical involvement of microRNAs in host immune defence against bacterial infection and that likewise the expression of the miRNAs is profoundly impacted by a variety of pathogens to subvert the immune response. Here, we report the role of hsa-let-7a miRNA in response to Staphylococcus epidermidis Small Colony Variants infection. We also assessed whether the expression levels of inflammatory cytokines associated with the hsa-let-7a are manipulated by the pathogen and the effect of the IFN-γ priming on the expression of hsa-let-7a and the fate of SCVs/WTs in infected macrophages. A striking observation was the downregulation of the let-7a miRNA upon challenge of the THP-1 activated cells with the SCV isolates while no significant changes in expression were noticed after the infection of macrophages with their WT counterparts. Staphylococcus epidermidis WT and SCV strains were found to invade and survive in macrophages. A significant reduction in bacterial load for both phenotypes was observed in macrophages treated with let-7a mimic compared to untreated ones. Survival of WTs was augmented in cells treated with the inhibitor in 4 out of 5 strains as compared to the number of bacteria recovered from non-transfected cells. At the same time, let-7a inhibitor did not influence on the survival of SCVs in macrophages as their number was comparable to number recovered from non-transfected cells. When the ratio of both let-7a cytokine targets was compared, anti-inflammatory IL-10 cytokine was induced by SCVs predominantly, while the macrophage challenge with WTs was characterized by the inflammatory cytokine profile with high IL-6 and low IL-10 production. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines has been expectedly retrieved when macrophages were transfected with let-7a mimic before infection with WT or SCV strains. The results also show that IFN-γ likely regulates the macrophage environment contributing to the inflammatory response and elimination of bacteria from intracellular milieu by augmenting the synthesis of pro-inflammatory cytokines and supressing the anti-inflammatory IL-10. Our work has shown that SCVs have the potential to regulate the let-7a miRNA to balance the pro-inflammatory IL-6 with anti-inflammatory IL-10 and this mechanism is one of the ways in a complex regulatory network adopted by SCVs to promote their survival.Agnieszka MagryśAgnieszka BogutElsevierarticleStaphylococcus epidermidisSmall Colony VariantsMicroRNAHsa-let-7aMacrophagesMicrobiologyQR1-502Other systems of medicineRZ201-999ENInternational Journal of Medical Microbiology, Vol 311, Iss 8, Pp 151542- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus epidermidis Small Colony Variants MicroRNA Hsa-let-7a Macrophages Microbiology QR1-502 Other systems of medicine RZ201-999
spellingShingle	Staphylococcus epidermidis Small Colony Variants MicroRNA Hsa-let-7a Macrophages Microbiology QR1-502 Other systems of medicine RZ201-999 Agnieszka Magryś Agnieszka Bogut MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses
description	Recent studies have provided emerging evidence of the critical involvement of microRNAs in host immune defence against bacterial infection and that likewise the expression of the miRNAs is profoundly impacted by a variety of pathogens to subvert the immune response. Here, we report the role of hsa-let-7a miRNA in response to Staphylococcus epidermidis Small Colony Variants infection. We also assessed whether the expression levels of inflammatory cytokines associated with the hsa-let-7a are manipulated by the pathogen and the effect of the IFN-γ priming on the expression of hsa-let-7a and the fate of SCVs/WTs in infected macrophages. A striking observation was the downregulation of the let-7a miRNA upon challenge of the THP-1 activated cells with the SCV isolates while no significant changes in expression were noticed after the infection of macrophages with their WT counterparts. Staphylococcus epidermidis WT and SCV strains were found to invade and survive in macrophages. A significant reduction in bacterial load for both phenotypes was observed in macrophages treated with let-7a mimic compared to untreated ones. Survival of WTs was augmented in cells treated with the inhibitor in 4 out of 5 strains as compared to the number of bacteria recovered from non-transfected cells. At the same time, let-7a inhibitor did not influence on the survival of SCVs in macrophages as their number was comparable to number recovered from non-transfected cells. When the ratio of both let-7a cytokine targets was compared, anti-inflammatory IL-10 cytokine was induced by SCVs predominantly, while the macrophage challenge with WTs was characterized by the inflammatory cytokine profile with high IL-6 and low IL-10 production. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines has been expectedly retrieved when macrophages were transfected with let-7a mimic before infection with WT or SCV strains. The results also show that IFN-γ likely regulates the macrophage environment contributing to the inflammatory response and elimination of bacteria from intracellular milieu by augmenting the synthesis of pro-inflammatory cytokines and supressing the anti-inflammatory IL-10. Our work has shown that SCVs have the potential to regulate the let-7a miRNA to balance the pro-inflammatory IL-6 with anti-inflammatory IL-10 and this mechanism is one of the ways in a complex regulatory network adopted by SCVs to promote their survival.
format	article
author	Agnieszka Magryś Agnieszka Bogut
author_facet	Agnieszka Magryś Agnieszka Bogut
author_sort	Agnieszka Magryś
title	MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses
title_short	MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses
title_full	MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses
title_fullStr	MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses
title_full_unstemmed	MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses
title_sort	microrna hsa-let-7a facilitates staphylococcal small colony variants survival in the thp-1 macrophages by reshaping inflammatory responses
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ce72f8ec134642da8899381526efc13c
work_keys_str_mv	AT agnieszkamagrys micrornahsalet7afacilitatesstaphylococcalsmallcolonyvariantssurvivalinthethp1macrophagesbyreshapinginflammatoryresponses AT agnieszkabogut micrornahsalet7afacilitatesstaphylococcalsmallcolonyvariantssurvivalinthethp1macrophagesbyreshapinginflammatoryresponses
_version_	1718400918787981312

MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses

Ejemplares similares