Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection

ABSTRACT Amebiasis is an enteric infection caused by Entamoeba histolytica, with symptoms ranging in severity from asymptomatic colonization to dysentery. Humans with the Q223R leptin receptor mutation have increased susceptibility to amebiasis, but the mechanism has been unclear. Using a mouse mode...

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Autores principales:	Caitlin Naylor, Stacey Burgess, Rajat Madan, Erica Buonomo, Khadija Razzaq, Katherine Ralston, William A. Petri
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ff2bab89cf9d4992a8546e2eb960f95a
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spelling	oai:doaj.org-article:ff2bab89cf9d4992a8546e2eb960f95a2021-11-15T15:47:03ZLeptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection10.1128/mBio.02046-142150-7511https://doaj.org/article/ff2bab89cf9d4992a8546e2eb960f95a2014-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02046-14https://doaj.org/toc/2150-7511ABSTRACT Amebiasis is an enteric infection caused by Entamoeba histolytica, with symptoms ranging in severity from asymptomatic colonization to dysentery. Humans with the Q223R leptin receptor mutation have increased susceptibility to amebiasis, but the mechanism has been unclear. Using a mouse model expressing the mutation, we tested the impact of the Q223R mutation on the innate immune response to E. histolytica infection. The 223R mutation resulted in delayed clearance of amebae from the cecum, as had been previously observed. We found that neutrophil influx to the site of the infection was reduced 12 h after infection in 223R mice. Depletion of neutrophils with anti-Ly6G monoclonal antibody increased susceptibility of wild-type mice to infection, supporting the importance of neutrophils in innate defense. Leptin expression was increased in the cecum by E. histolytica infection, suggesting that leptin could serve as a homing signal for neutrophils to the gut. Interestingly, neutrophils from mice with the 223R mutation had diminished chemotaxis toward leptin. This impaired chemotaxis likely explained the reduced gut infiltration of neutrophils. The newly recognized effect of the leptin receptor Q223R mutation on neutrophil chemotaxis and the impact of this mutation on multiple infectious diseases suggest a broader impact of this mutation on susceptibility to disease. IMPORTANCE The Q223R leptin receptor mutation results in increased susceptibility of children and adults to E. histolytica, one of the leading causes of diarrhea morbidity and mortality in children of the developing world. Here we show that the mutation results in reduced neutrophil infiltration to the site of infection. This decreased infiltration is likely due to the mutation’s impact on neutrophil chemotaxis toward leptin, an inflammatory agent upregulated in the cecum after infection. The significance of this work thus extends beyond understanding E. histolytica susceptibility by also providing insight into the potential impact of leptin on neutrophil function in other states of altered leptin signaling, which include both malnutrition and obesity.Caitlin NaylorStacey BurgessRajat MadanErica BuonomoKhadija RazzaqKatherine RalstonWilliam A. PetriAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 6 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Caitlin Naylor Stacey Burgess Rajat Madan Erica Buonomo Khadija Razzaq Katherine Ralston William A. Petri Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection
description	ABSTRACT Amebiasis is an enteric infection caused by Entamoeba histolytica, with symptoms ranging in severity from asymptomatic colonization to dysentery. Humans with the Q223R leptin receptor mutation have increased susceptibility to amebiasis, but the mechanism has been unclear. Using a mouse model expressing the mutation, we tested the impact of the Q223R mutation on the innate immune response to E. histolytica infection. The 223R mutation resulted in delayed clearance of amebae from the cecum, as had been previously observed. We found that neutrophil influx to the site of the infection was reduced 12 h after infection in 223R mice. Depletion of neutrophils with anti-Ly6G monoclonal antibody increased susceptibility of wild-type mice to infection, supporting the importance of neutrophils in innate defense. Leptin expression was increased in the cecum by E. histolytica infection, suggesting that leptin could serve as a homing signal for neutrophils to the gut. Interestingly, neutrophils from mice with the 223R mutation had diminished chemotaxis toward leptin. This impaired chemotaxis likely explained the reduced gut infiltration of neutrophils. The newly recognized effect of the leptin receptor Q223R mutation on neutrophil chemotaxis and the impact of this mutation on multiple infectious diseases suggest a broader impact of this mutation on susceptibility to disease. IMPORTANCE The Q223R leptin receptor mutation results in increased susceptibility of children and adults to E. histolytica, one of the leading causes of diarrhea morbidity and mortality in children of the developing world. Here we show that the mutation results in reduced neutrophil infiltration to the site of infection. This decreased infiltration is likely due to the mutation’s impact on neutrophil chemotaxis toward leptin, an inflammatory agent upregulated in the cecum after infection. The significance of this work thus extends beyond understanding E. histolytica susceptibility by also providing insight into the potential impact of leptin on neutrophil function in other states of altered leptin signaling, which include both malnutrition and obesity.
format	article
author	Caitlin Naylor Stacey Burgess Rajat Madan Erica Buonomo Khadija Razzaq Katherine Ralston William A. Petri
author_facet	Caitlin Naylor Stacey Burgess Rajat Madan Erica Buonomo Khadija Razzaq Katherine Ralston William A. Petri
author_sort	Caitlin Naylor
title	Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection
title_short	Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection
title_full	Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection
title_fullStr	Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection
title_full_unstemmed	Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection
title_sort	leptin receptor mutation results in defective neutrophil recruitment to the colon during <named-content content-type="genus-species">entamoeba histolytica</named-content> infection
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/ff2bab89cf9d4992a8546e2eb960f95a
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Leptin Receptor Mutation Results in Defective Neutrophil Recruitment to the Colon during <named-content content-type="genus-species">Entamoeba histolytica</named-content> Infection

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