IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients

Abstract

SUMMARYIL-5 is a major factor inducing differentiation of B lymphocytes into immunoglobulin-producing cells as well as a main regulator of eosinophils. Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with alveolar echinococcosis (AE) express IL-5 mRNA after stimulation with crude Echinococcus multilocularis (E.m.) antigen. To characterize the observed response in lymphocyte subpopulations, we cultured patients' PBMC in the presence of E.m. crude antigen for 18 h. PBMC were separated from seven patients by fluorescence-activated cell sorting (EPICSorter) into CD4 + and CD8 + subpopulations and from an additional seven patients by magnetic cell sorting (MACS) into CD4 + , CD8 + and the CD4 + /CD8 + depleted fractions. mRNA was detected by reverse transcriptasepolymerase chain reaction (RT-PCR) for the cytokines IFN-g, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, as well as for b-actin as control. IL-4 and IFN-g expression was positive in all of the patients in the stimulated CD4 + subgroup. IL-5 mRNA expression was detected in eight out of 14 CD4 + samples (58%) and not observed in the other subpopulations, or the unstimulated and healthy controls. Co-expression of other Th2 cytokines in the eight patients expressing IL-5 mRNA was found in five patients for IL-3 and in seven for IL-10. Expression of IL-5 and both Th2 cytokines (IL-3 and IL-10) was only observed in patients judged as critically ill. Out of the six patients who were regarded as cured after radical operation or as stabilized with or without chemotherapy, only two expressed IL-5. Out of those eight patients considered as critically ill, six expressed IL-5 mRNA and five of these co-expressed IL-3 and IL-10. Thus, we conclude that specific antigenic challenge of PBMC from patients with active or previous AE induces an IL-5 response of CD4 + lymphocytes. The expression of Th2-type interleukin mRNA is significantly more frequent in patients clinically judged as progressive. Furthermore, IgE was elevated only in patients regarded as critically ill (six out of eight). In none of the patients were eosinophils elevated. These data support a Th2-type immune response in patients with chronic E. multilocularis infection.

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. I. Comparison of patients with progressive and abortive lesions

“…As no major differences were observed in the present study, the differences in the cytokine response of both types of patients could not be explained by variations in their mitotic responsiveness to antigenic stimulation. IL-5 has been shown to be specifically stimulated by E. multilocularis antigens in progressive AE [8,9]. In this study, mRNA semiquantification showed that there was no significant difference in IL-5 mRNA expression between subjects with an efficient immune response against the parasite and patients who developed progressive AE.…”

“…The higher increase in IL‐5 production observed in patients with progressive AE could be enhanced by a particular genetic background; the increase seems to be the consequence of an expanding IL‐5‐secreting cell population: we [10] and Jenne et al . [9] demonstrated that this secretion of IL‐5 was restricted to CD4 + T lymphocytes in human AE. Echinococcus multilocularis antigenic preparations could regulate the expression of IL‐5 gene at the post‐transcriptional level, as suggested by the results of IL‐5 mRNA expression.…”

Cytokine gene expression in peripheral blood mononuclear cells (PBMC) from patients with pharmacologically treated cystic echinococcosis

“…In many chronic infections the clinical outcome of the disease is associated with Th1 or Th2 cell activation. In most helminthic infections the healing or protection is related to Th2 cell activation [13][14][15], even if some infections, including trichinellosis, schistosomiasis, and cystic and alveolar echinococcosis, display Th2-mediated susceptibility [6,7,[16][17][18][19].…”

Albendazole increases the inflammatory response and the amount of Em2-positive small particles of Echinococcus multilocularis (spems) in human hepatic alveolar echinococcosis lesions

“…The complex immune response during infection is characterized by an abnormal production of various interleukins, such as interleukin-5 [19,20], IL-27 [21], high levels of IL-10 and TGF-beta [18,22]. Simultaneously, insufficient production of IL-12 [23], IL-31, IL-33 [21], IFN-gamma and cytotoxic T cells leads to an enhanced tolerance towards the parasite.…”