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.
Highlights
Eosinophils are regarded as terminally differentiated nonreplicating effector cells that accumulate in a number of health disorders, including parasitic infections and allergic diseases [1], where they may play a beneficial role in the host defence against helminth infections [2], or cause a harmful inflammatory response [3], respectively
In mice infected with Schistosoma mansoni, eosinophils have been associated with Th-2 polarization by IL-4 production [23] and can be a dominant source of Th-2 type cytokines [24]
When we examined cytokine production in response to Schistosoma mansoni adult worm antigen (SWA), levels of Th-2 type cytokines (IL-4, IL-5 and IL-13) were highest in cultures of peripheral blood mononuclear cell (PBMC) alone, significantly lower in PBMC + eosinophil co-culture supernatants and lowest in cultures of eosinophils alone (Figure 1a–c)
Summary
Eosinophils are regarded as terminally differentiated nonreplicating effector cells that accumulate in a number of health disorders, including parasitic infections and allergic diseases [1], where they may play a beneficial role in the host defence against helminth infections [2], or cause a harmful inflammatory response [3], respectively. There is growing evidence that eosinophils play an additional role of immunoregulation [15] in both adaptive and innate immunity to parasitic infections. Evidence of the ability of eosinophils to regulate T-cell function has been reviewed [15,19], highlighting the role of eosinophils in both innate and adaptive immunity. Eosinophils express both Th-1 (IFN-c, IL-2) and Th-2 (IL-4, IL-5, IL-13) cytokines [20,21,22]. In mice infected with Schistosoma mansoni, eosinophils have been associated with Th-2 polarization by IL-4 production [23] and can be a dominant source of Th-2 type cytokines [24]
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