Activated Eosinophils Are the Major Source of Th2-Associated Cytokines in the Schistosome Granuloma

Abstract

Eosinophils are a numerically dominant cell population within the schistosome granuloma. These granuloma eosinophils can produce a variety of cytokines, including IL-2, IL-4, IL-5, and IFN-γ. Therefore, eosinophils may play a key role in the determination of the unique cytokine microenvironment within the granuloma milieu. These studies investigated the potential role of eosinophils in the regulation of granuloma immunopathology. We have characterized spleen- and granuloma-derived eosinophils based on cellular activation and cytokine production during the development of murine schistosomiasis. Based on the criteria of hypodensity and CD69 expression, granuloma eosinophils were highly activated and very homogeneous at 7 and 11 wk postinfection. Splenic eosinophils were also activated at 7 wk postinfection, but were much more heterogeneous than their granuloma counterparts. By 11 wk postinfection, few hypodense splenic eosinophils were observed. Eosinophils represented the majority of cytokine-producing cells in the granuloma and were a dominant source of IL-4. Eosinophils also produced IL-2, IL-5, and IFN-γ, using the criteria of mRNA in situ hybridization and intracellular cytokine staining by FACS. Granuloma eosinophil activation and cytokine production were greatest at the time of maximum granuloma formation, i.e., 10–12 wk after initial cercarial exposure. Therefore, locally activated eosinophils, not Th2 lymphocytes, produce the majority of Th2 cytokines in the granuloma milieu and may be important determinators of immunopathology in schistosomiasis.

Profile of T and B lymphocytes in individuals resistant to Schistosoma mansoni infection

“…Among the hematological evaluation data, eosinophilia was the only parameter that differed between groups. The increase in the absolute number of eosinophils observed in the group with a high parasite load is associated with the pattern of Th2 response to helminthic infection, with production of the cytokines IL-4, IL-5, and IL-13 (Rumbley et al 1999). It should be noted that IL-5 is considered the most important cell growth factor for eosinophils, which participates in the process of maturation and increased survival of eosinophils.…”

Eosinophiles, parasites et allergie : de la biologie à la clinique

“…Dans ce modèle, les larves sont recouvertes d 'éosinophiles et de macrophages, un phénom ène ressemblant au mécanisme d 'ADCC, observé autour de larves de Schistosom a mansoni, en présence d 'éosinophiles ou de m acrophages et d 'anticorps IgE. C 'est également dans ce modèle qu'il a été démontré que les éosinophiles présents dans le gra nulome produisaient différentes cytokines, dont l'IL-2, l'IL-4, l'IL-5 et l'IFN γ, (Rumbley et al, 1999) confir m ant ainsi les observations réalisées chez l'Hom m e (W oerly et al, 1999).…”

Eosinophil‐derived interferon‐γ drives transmembrane protein 119–induced new bone formation in chronic rhinosinusitis with nasal polyps

“…Tissue eosinophils are a hallmark of Th2 inflammation mediated by interleukin (IL) 4, IL‐5, and IL‐13 10,11 . Eosinophils can produce various cytokines, chemokines, and lipid mediators, resulting in tissue damage and airway remodeling in patients with CRS and asthma 12–16 .…”

“…Tissue eosinophils are a hallmark of Th2 inflammation mediated by interleukin (IL) 4, IL-5, and IL-13. 10,11 Eosinophils can produce various cytokines, chemokines, and lipid mediators, resulting in tissue damage and airway remodeling in patients with CRS and asthma. [12][13][14][15][16] Interferon-γ (IFN-γ), a representative cytokine of Th1 cells, is secreted by eosinophils 17,18 and is higher in patients with CRSwNP than controls.…”