Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro

Abstract

SummaryHigh numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno‐regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th‐2 type cytokines interleukin (IL)‐4, IL‐5 and IL‐13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC‐only cultures stimulated with SWA. Substantial levels of IL‐13, IL‐10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil‐induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th‐2 type cytokines. This study shows that eosinophils may down‐modulate schistosome‐specific Th‐2 type cytokine responses in S. mansoni‐infected individuals. The mechanism of this immune modulation remains to be elucidated.

Histological assessment of granulomas in natural and experimental Schistosoma mansoni infections using whole slide imaging

“…More recently, several studies have changed the view of eosinophils as cytotoxic effector cells towards an immune-regulatory role in both adaptive and innate immunity to parasite infections, including schistosomiasis mansoni [ 26 , 43 ]. Therefore, the function of eosinophils in this pathology still remains unclear and controversial.…”

Identification of Piecemeal Degranulation and Vesicular Transport of MBP-1 in Liver-Infiltrating Mouse Eosinophils During Acute Experimental Schistosoma mansoni Infection

“…There is considerable debate on the role of eosinophils during schistosomiasis. It remains uncertain if eosinophils act as major effector cells against the parasite; as immunomodulators of the immune response; as participants in tissue homeostasis and metabolism, which could favor establishment and maintenance of parasitic worms in their hosts, or merely as operators in remodeling and clearance of debris following injury (7, 10–14).…”

Schistosoma Infection and Schistosoma-Derived Products Modulate the Immune Responses Associated with Protection against Type 2 Diabetes

“…In fact, levels of Th2 cytokines (IL-4, IL-5, and IL-13) produced in response to S. mansoni adult worm antigen (SWA) in vitro were highest in cultures of human peripheral blood mononuclear cells (PBMCs) alone, and considerably lower than those in the supernatants of PBMC + eosinophil cocultures; moreover, they were lowest in cultures of eosinophils alone. This study showed that eosinophils down-modulate the Schistosoma -specific Th2 cytokine response in S. mansoni- infected individuals ( 34 ). Hams et al ( 35 ) reported that recombinant S. mansoni egg-derived ω-1 improves the metabolic status of obese mice, and that this is mediated by the release of cytokine IL-33, which initiates the recruitment of eosinophils in AT.…”