Basophils help establish protective immunity induced by irradiated larval vaccination for filariasis

Abstract

Basophils are increasingly recognized as playing important roles in the immune response towards helminths. In this study, we evaluated the role of basophils in vaccine-mediated protection against filariae, tissue-invasive parasitic nematodes responsible for diseases such as elephantiasis and river blindness. Protective immunity and immunological responses were assessed in BALB/c mice vaccinated with irradiated L3 stage larvae and depleted of basophils with weekly injections of anti-CD200R3 antibody. Depletion of basophils after administration of the vaccination regimen but before challenge infection did not alter protective immunity. In contrast, basophil depletion initiated prior to vaccination and continued after challenge infection significantly attenuated the protective effect conferred by vaccination. Vaccine-induced cellular immune responses to parasite antigen were substantially decreased in basophil-depleted mice, with significant decreases in CD4+ T-cell production of IL-4, IL-5, IL-10, and IFN-γ. Interestingly, skin mast cell numbers, which increased significantly after vaccination with irradiated L3 larvae, were unchanged after vaccination in basophil-depleted mice. These findings demonstrate that basophils help establish the immune responses responsible for irradiated L3 vaccine protection.

Multifaceted roles of basophils in health and disease

“…80 Basophils also contribute to protection against the filarial nematode Litomosoides sigmodontis when mice were immunized with irradiated larvae. 81 Thus basophils play a critical role in acquired immunity against helminth infections. Basophils also show some contribution in mice to the protective immunity in primary infection with Strongyloides ratti or Strongyloides venezuelensis.…”

Looking beyond the induction of Th2 responses to explain immunomodulation by helminths

“…Basophils are an important component of the immune response to helminth infections . Basophils gained prominence because of their potential role in Th2 cell differentiation as the initial source of ‘innate’ IL‐4 that was capable of driving a Th2 response in murine models of helminth infection but also of inducing AAMs.…”

Basophils Are Dispensable for the Control of a Filarial Infection

“…Despite previous studies using depleting Abs that suggested a role of basophils during Th2 T cell priming, Th2 T cell expansion was not affected in (22). During infection with L. sigmodontis, basophils were reported to participate in the protective immunity induced by vaccination with irradiated larvae, which results in a 70% reduction of the worm burden (12). We evaluated the establishment of immunity induced by vectortransmitted L3 to mimic the natural situation.…”

“…During infection with the tissue-dwelling L. sigmodontis, basophils were proposed to amplify the type 2 immune response without having an impact on the course of primary infection (11). However, depletion of basophils prior to vaccination with irradiated larvae altered the worm burden in a challenge infection (12), suggesting a central role for basophils in immune memory formation to tissue dwelling helminths.…”