IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis

Abstract

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodonitis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5.

B-Cell Deficiency Suppresses Vaccine-Induced Protection against Murine Filariasis but Does Not Increase the Recovery Rate for Primary Infection

“…The kinetics of the recovery rate have been well defined in the L. sigmodontis mouse model; as observed in other experimental filarial systems (6), the recovery rate drops a few hours after challenge inoculation (phase 1) and then remains stable (phase 2) for 2 months (24,26,29). In BALB/c mice vaccinated with irradiated larvae, the recovery rate follows the same kinetics; however, there is a stronger reduction during phase 1, amounting to 65 to 70% protection (24,29).…”

Blood-feeding in the young adult filarial wormsLitomosoides sigmodontis

“…However, as suggested by studies on suckling rats (Zhang et al 2001), other pathways might occur in the digestive tract. A correlation between IL-5 production and growth (Martin et al 2000 a, b;Babayan et al 2003) had been suggested during the larval stages. Haematophagy, however, seems to be a characteristic of the adult stage and may contribute to sexual maturation and thus the fitness of L. sigmodontis with its hosts.…”

CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry

“…It is known that L3, after transmission into the skin of mice, migrate via the lymphatics (27)(28)(29) into the pleural space. Accordingly, CCL17 expression was detected not only upon artificial stimulation of BMDCs but also in CD11 + DCs in the skin, in the draining lymph nodes and the lung after natural filarial infection.…”