Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA

Abstract Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica...

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Autores principales:	Yasmin Cabral Moreira, Maele Jordão, Oscar Tadeu Ferreira da Costa, Elizangela Farias, Alysson Guimaraes Costa, Viviane de Farias, Dorval Antonio Mafra Coimbra, Tatiana Bacry Cardoza, Yury Oliveira Chaves, Patricia Puccinelli Orlandi, Fabio Trindade Maranhão Costa, Paulo Afonso Nogueira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ab01836709a47d28db43af9325ac56f
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spelling	oai:doaj.org-article:0ab01836709a47d28db43af9325ac56f2021-12-02T14:06:11ZEvents associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA10.1038/s41598-021-82330-02045-2322https://doaj.org/article/0ab01836709a47d28db43af9325ac56f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82330-0https://doaj.org/toc/2045-2322Abstract Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.Yasmin Cabral MoreiraMaele JordãoOscar Tadeu Ferreira da CostaElizangela FariasAlysson Guimaraes CostaViviane de FariasDorval Antonio Mafra CoimbraTatiana Bacry CardozaYury Oliveira ChavesPatricia Puccinelli OrlandiFabio Trindade Maranhão CostaPaulo Afonso NogueiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasmin Cabral Moreira Maele Jordão Oscar Tadeu Ferreira da Costa Elizangela Farias Alysson Guimaraes Costa Viviane de Farias Dorval Antonio Mafra Coimbra Tatiana Bacry Cardoza Yury Oliveira Chaves Patricia Puccinelli Orlandi Fabio Trindade Maranhão Costa Paulo Afonso Nogueira Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA
description	Abstract Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.
format	article
author	Yasmin Cabral Moreira Maele Jordão Oscar Tadeu Ferreira da Costa Elizangela Farias Alysson Guimaraes Costa Viviane de Farias Dorval Antonio Mafra Coimbra Tatiana Bacry Cardoza Yury Oliveira Chaves Patricia Puccinelli Orlandi Fabio Trindade Maranhão Costa Paulo Afonso Nogueira
author_facet	Yasmin Cabral Moreira Maele Jordão Oscar Tadeu Ferreira da Costa Elizangela Farias Alysson Guimaraes Costa Viviane de Farias Dorval Antonio Mafra Coimbra Tatiana Bacry Cardoza Yury Oliveira Chaves Patricia Puccinelli Orlandi Fabio Trindade Maranhão Costa Paulo Afonso Nogueira
author_sort	Yasmin Cabral Moreira
title	Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA
title_short	Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA
title_full	Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA
title_fullStr	Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA
title_full_unstemmed	Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA
title_sort	events associated with susceptibility to invasive salmonella enterica serovar typhi in balb/c mice previously infected with plasmodium berghei anka
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0ab01836709a47d28db43af9325ac56f
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Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA

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