Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.

Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These sym...

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Autores principales:	Stacey L Burgess, Akihiko Oka, Bo Liu, David T Bolick, David Noah Oakland, Richard L Guerrant, Luther Bartelt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2019
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/9500da7ed4804102babefd82b74752fd
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spelling	oai:doaj.org-article:9500da7ed4804102babefd82b74752fd2021-12-02T20:24:12ZIntestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.1935-27271935-273510.1371/journal.pntd.0007515https://doaj.org/article/9500da7ed4804102babefd82b74752fd2019-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0007515https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection.Stacey L BurgessAkihiko OkaBo LiuDavid T BolickDavid Noah OaklandRichard L GuerrantLuther BarteltPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 13, Iss 7, p e0007515 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Stacey L Burgess Akihiko Oka Bo Liu David T Bolick David Noah Oakland Richard L Guerrant Luther Bartelt Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
description	Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection.
format	article
author	Stacey L Burgess Akihiko Oka Bo Liu David T Bolick David Noah Oakland Richard L Guerrant Luther Bartelt
author_facet	Stacey L Burgess Akihiko Oka Bo Liu David T Bolick David Noah Oakland Richard L Guerrant Luther Bartelt
author_sort	Stacey L Burgess
title	Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
title_short	Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
title_full	Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
title_fullStr	Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
title_full_unstemmed	Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
title_sort	intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.
publisher	Public Library of Science (PLoS)
publishDate	2019
url	https://doaj.org/article/9500da7ed4804102babefd82b74752fd
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_version_	1718374064186195968

Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.

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