The Journal of Immunology, 2007, 178: 2609.
Copyright © 2007 by The American Association of Immunologists, Inc.
Comment on "Local CD11c+ MHC Class II– Precursors Generate Lung Dendritic Cells during Respiratory Viral Infection, but Are Depleted in the Process"
Christophe von Garnier*,
,
Deborah Strickland* and
Philip Stumbles*,
* Telethon Institute for Child Health Research and Centre for Child Health Research, School of Pediatrics and Child Health, University of Western Australia, Perth, Australia
Department of Respiratory Medicine, Berne University Hospital, Berne, Switzerland
Division of Health Sciences, Murdoch University, Perth, Australia
In their recent paper, Wang et al. (1) reported that lung dendritic cell (DC) precursors are depleted during respiratory syncytial viral (RSV) infection.
Several lines of evidence, however, suggest that the CD11c+ MHC class II– cells the authors described as DC precursors depleted during RSV infection likely are alveolar and/or interstitial macrophages: first, in a recent detailed multiparameter approach to characterize APCs within the respiratory tract, we showed that a CD11c+MHCII– cell population in the lung parenchyma expresses the macrophage marker F4/80+, is CD11b–, is highly endocytic, poorly induces T cell activation, and has morphological features of alveolar macrophages (2). In naive BALB/c mice, this population represents 
6 ± 0.5% of the total cells obtained from lung parenchymal digests, closely correlating with the frequency of 6% stated by the authors for their putative DC precursor. Second, it has previously been shown that viral infection induces excessive macrophage apoptosis, thus providing a plausible explanation for the depletion of the alveolar macrophages, and not the DC precursor population, during RSV infection (3). Third, based on electron microscopical ultrastructure as well as repopulation kinetics following irradiation and dexamethasone treatment, we have previously identified a candidate resident CD11clowMHC II–CD11b+ precursor DC in the lung parenchyma (2). Finally, the authors fail to explain the paradox that their so-called DC precursors are depleted yet CD11c+MHCII+ lung DC are increased during viral infection—one would expect that depletion of precursor would result in lower DC numbers, unless there is greatly enhanced differentiation from precursors to DCs.
These studies highlight the complexity of APC populations within respiratory tract compartments requiring a multiparameter approach of surface marker expression, functional and ultrastructural analyses to enable accurate identification of DC and other specific cell types, especially during complex inflammatory conditions.
References
- Wang, H., N. Peters, V. Laza-Stanca, N. Nawroly, S. L. Johnston, J. Schwarze. 2006. Local CD11c+ MHC class II– precursors generate lung dendritic cells during respiratory viral infection, but are depleted in the process. J. Immunol. 177: 2536-2542. [Abstract/Free Full Text]
- von Garnier, C., L. Filgueira, M. Wikstrom, M. Smith, J. A. Thomas, D. H. Strickland, P. G. Holt, P. A. Stumbles. 2005. Anatomical location determines the distribution and function of dendritic cells and other APCs in the respiratory tract. J. Immunol. 175: 1609-1618. [Abstract/Free Full Text]
- Tyner, J. W., O. Uchida, N. Kajiwara, E. Y. Kim, A. C. Patel, M. P. O’Sullivan, M. J. Walter, R. A. Schwendener, D. N. Cook, T. M. Danoff, et al 2005. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat. Med. 11: 1180-1187. [Medline]
