Depletion of alveolar macrophages in cd11c diphtheria toxin receptor mice produces an inflammatory response

Lydia M. Roberts, Hannah E. Ledvina, Shraddha Tuladhar, Deepa Rana, Shaun P. Steele, Gregory D. Sempowski, Jeffrey A Frelinger

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c. DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalImmunity Inflammation and Disease
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Alveolar Macrophages
Diphtheria Toxin
Francisella
Francisella tularensis
Intranasal Administration
Lung
Adaptive Immunity
Allergy and Immunology
Chemokines
Innate Immunity
Primates
Neutrophils
Spleen
Research Personnel
Heparin-binding EGF-like Growth Factor
Cytokines
Therapeutics

Keywords

  • Alveolar macrophage
  • Animal models
  • CD11c diphtheria toxin receptor mice
  • Lung
  • Neutrophil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Depletion of alveolar macrophages in cd11c diphtheria toxin receptor mice produces an inflammatory response. / Roberts, Lydia M.; Ledvina, Hannah E.; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P.; Sempowski, Gregory D.; Frelinger, Jeffrey A.

In: Immunity Inflammation and Disease, Vol. 3, No. 2, 01.01.2015, p. 71-81.

Research output: Contribution to journalArticle

Roberts, Lydia M. ; Ledvina, Hannah E. ; Tuladhar, Shraddha ; Rana, Deepa ; Steele, Shaun P. ; Sempowski, Gregory D. ; Frelinger, Jeffrey A. / Depletion of alveolar macrophages in cd11c diphtheria toxin receptor mice produces an inflammatory response. In: Immunity Inflammation and Disease. 2015 ; Vol. 3, No. 2. pp. 71-81.
@article{11d827d19da44a0aad4205580b56c70a,
title = "Depletion of alveolar macrophages in cd11c diphtheria toxin receptor mice produces an inflammatory response",
abstract = "Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c. DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data.",
keywords = "Alveolar macrophage, Animal models, CD11c diphtheria toxin receptor mice, Lung, Neutrophil",
author = "Roberts, {Lydia M.} and Ledvina, {Hannah E.} and Shraddha Tuladhar and Deepa Rana and Steele, {Shaun P.} and Sempowski, {Gregory D.} and Frelinger, {Jeffrey A}",
year = "2015",
month = "1",
day = "1",
doi = "10.1002/iid3.51",
language = "English (US)",
volume = "3",
pages = "71--81",
journal = "Immunity, inflammation and disease",
issn = "2050-4527",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Depletion of alveolar macrophages in cd11c diphtheria toxin receptor mice produces an inflammatory response

AU - Roberts, Lydia M.

AU - Ledvina, Hannah E.

AU - Tuladhar, Shraddha

AU - Rana, Deepa

AU - Steele, Shaun P.

AU - Sempowski, Gregory D.

AU - Frelinger, Jeffrey A

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c. DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data.

AB - Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c. DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data.

KW - Alveolar macrophage

KW - Animal models

KW - CD11c diphtheria toxin receptor mice

KW - Lung

KW - Neutrophil

UR - http://www.scopus.com/inward/record.url?scp=84949558305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949558305&partnerID=8YFLogxK

U2 - 10.1002/iid3.51

DO - 10.1002/iid3.51

M3 - Article

VL - 3

SP - 71

EP - 81

JO - Immunity, inflammation and disease

JF - Immunity, inflammation and disease

SN - 2050-4527

IS - 2

ER -