Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

Immunity, Inflammation and Disease

Lydia M. Roberts¹  Hannah E. Ledvina¹  Shraddha Tuladhar¹  Deepa Rana¹  Shaun P. Steele³  Gregory D. Sempowski² 

[1] Department of Immunobiology, University of Arizona, Tucson, Arizona, USA;Duke Human Vaccine Institute, Durham, North Carolina, USA;Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

关键词: Alveolar macrophage;    animal models;    CD11c diphtheria toxin receptor mice;    lung;    neutrophil;   

DOI  :  10.1002/iid3.51

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Immunity, Inflammation and DiseasePublished by John Wiley & Sons Ltd.

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