Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response. Issue 2 (23rd March 2015)

• Record Type: Journal Article
• Authors: Roberts, Lydia M.; Ledvina, Hannah E.; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P.; Sempowski, Gregory D.; Frelinger, Jeffrey A.
• Is Part Of: Immunity, inflammation and disease. Volume 3:Issue 2(2015)
• Page Start: 71
• Page End: 81
• Publication Date: 2015-03-23
• Subjects: Alveolar macrophage -- animal models -- CD11c diphtheria toxin receptor mice -- lung -- neutrophil; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.51
• Languages: English
• ISSNs: 2050-4527

Abstract

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. Abstract : Intranasal treatment of CD11c.DOG mice with diphtheria toxin depletes alveolar macrophages while leaving systemic dendritic cells intact. However, alveolar macrophage depletion is accompanied by numerous changes to the cellular composition and cytokine milieu of the lung. The multitude of changes after diphtheria toxin treatment rendered it impossible to effectively differentiate differences seen in the immune response due to the loss of alveolar macrophages and serve as a cautionary tale for other researchers using this model.