Wuchereria bancrofti-infected individuals harbor distinct IL-10-producing regulatory B and T cell subsets which are affected by anti-filarial treatment

Abstract

Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical symptoms and present a tightly regulated immune system characterized by higher frequencies of regulatory T cells (Treg), suppressed proliferation and Th2 cytokine responses accompanied with increased secretion of IL-10, TGF-β and infection-specific IgG4. Nevertheless, the filarial-induced modulation of the host`s immune system and especially the role of regulatory immune cells like regulatory B (Breg) and Treg during an ongoing LF infection remains unknown. Thus, we analysed Breg and Treg frequencies in peripheral blood from Ghanaian uninfected endemic normals (EN), lymphedema (LE), asymptomatic patent (CFA+MF+) and latent (CFA+MF-) W . bancrofti -infected individuals as well as individuals who were previously infected with W . bancrofti (PI) but had cleared the infection due to the administration of ivermectin (IVM) and albendazole (ALB). In summary, we observed that IL-10-producing CD19 + CD24 high CD38d high Breg were specifically increased in patently infected (CFA+MF+) individuals. In addition, CD19 + CD24 high CD5 + CD1d high and CD19 + CD5 + CD1d high IL-10 + Breg as well as CD4 + CD127 - FOXP3 + Treg frequencies were significantly increased in both W . bancrofti -infected cohorts (CFA+MF+ and CFA+MF-). Interestingly, the PI cohort presented frequency levels of all studied regulatory immune cell populations comparable with the EN group. In conclusion, the results from this study show that an ongoing W . bancrofti infection induces distinct Breg and Treg populations in peripheral blood from Ghanaian volunteers. Those regulatory immune cell populations might contribute to the regulated state of the host immune system and are probably important for the survival and fertility (microfilaria release) of the helminth.

Comparison of immune responses to Loa loa stage-specific antigen extracts in Loa loa-exposed BALB/c mice upon clearance of infection

“…Indeed, we did not isolate any L. loa developmental stages 42 days pi which was reflected in the relatively comparable levels of systemic cytokine, chemokine and immunoglobulins between the infected groups. In accordance with these findings, we recently showed that systemic regulatory immune cell frequencies (regulatory B cells) had returned to basal levels in humans who cleared Wuchereria bancrofti infection due to anti-filarial treatment compared to uninfected endemic normals [37]. In association, some results did indicate a change in B cell activity since IgM and IgG levels in groups exposed to adult worms were lower than other groups which was accompanied by higher IL-27 (enhances germinal center B cell activity) [38] and IL-9 (IL-9R signalling in memory B cells regulates humoral recall responses) [39].…”

“…Interestingly, re-stimulation of L3-exposed splenocytes with L3 antigen extract significantly induced IL-10 and CXCL1 secretion. However, IL-10 secretion was also induced in splenocytes upon L5, adult worm and MF antigen extract by tendency, confirming that chronic filarial infections are characterized by a dominate regulatory environment involving the secretion of IL-10 [17][18][19]37]. In addition, several studies have shown that neutrophil activation play an important role for protective immunity against L3 [51][52][53][54][55], suggesting that the neutrophil-specific chemokine CXCL1 might be involved as well.…”

Impact of Helminth Infections on Female Reproductive Health and Associated Diseases

“…Helminth-induced immune modulation benefits parasite survival by supporting asymptomatic or chronic infections. This has been demonstrated by individuals with asymptomatic lymphatic filariasis who display regulatory T and B cell responses (58), as well as skewed Th2 and regulatory T cell cytokine profiles i.e. favorable IL-4 and TGF-b, over IFN-g and IL-17 production (46,(59)(60)(61).…”

Th1/Th2/Th17 cytokine profile in hepatic cystic Echinococcosis patients with different cyst stages

“…48,49 Moreover, B cells, especially regulatory and memory B cells, modulate the host's immune response via the production of IL-10. 50 Importantly, in addition to close association with Th2 responses, IL-10 production may play significant roles in the activation process of the inhibitory immune response during helminth infection. 51,52 Thus, it is hypothesized that other cells, especially regulatory T and B cells, may contribute to the cytokine pool during E. granulosus s.l.…”