We read with great interest the article by del Fresno et al. in the May 15, 2009 issue of The Journal of Immunology (1). This elegant study showed that ex vivo circulating monocytes from cystic fibrosis patients exhibit a tolerant IL-12lowIL-23lowIL-10high phenotype of monocytes after LPS challenge with low Ag presentation capacity, which is suggestive of a M2 phenotype.

One of the main features of cystic fibrosis patients is a deregulated clearance of infections at the nasal mucosa and lung levels. Pathogen clearance is controlled by the innate immune system, and the macrophage activation status is crucial for an efficient response. The concept of macrophage activation reflects their different functionality (2). In nasal tissue of patients with cystic fibrosis we observed by immunohistochemistry an accumulation of CD14+ cells without an apparent increase in CD68+, CD206+, or CD163+ cells. Thus, in contrast to what was described by del Fresno et al. (1), the inflammatory profile in nasal polyp tissue of cystic fibrosis patients with low levels of IL-2Ra and high levels of IL-1β, IL-6, and TNF (3, 4) favors the M1 phenotype of macrophages.

This is in contrast with adult bilateral eosinophilic nasal polyps, which do show increased levels of CD163+CD206+ M2-type macrophages within the tissue, whereas CD14+ cells are not increased compared with controls. However, such differences cannot be seen in the peripheral blood of the same patients.

These data suggest that the macrophage activation status may differ depending on the compartment and may not be generalized.

del Fresno, C., F. García-Rio, V. Gómez-Piña, A. Soares-Schanoski, I. Fernández-Ruíz, T. Jurado, T. Kajiji, C. Shu, E. Marín, A. Gutierrez del Arroyo, et al
. Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: demonstration in isolated monocytes from cystic fibrosis patients.
J. Immunol.
Mantovani, A., S. Sozzani, M. Locati, P. Allavena, A. Sica.
. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes.
Trends Immunol.
Claeys, S., H. Van Hoecke, G. Holtappels, P. Gevaert, T. De Belder, B. Verhasselt, P. Van Cauwenberge, C. Bachert.
. Nasal polyps in patients with and without cystic fibrosis: a differentiation by innate markers and inflammatory mediators.
Clin. Exp. Allergy
Van Zele, T., S. Claeys, P. Gevaert, G. Van Maele, G. Holtappels, P. Van Cauwenberge, C. Bachert.
. Differentiation of chronic sinus diseases by measurement of inflammatory mediators.