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

Abstract

To establish the role of B cells and antibodies in destroying filariae, mice lacking mature B cells and therefore unable to produce antibodies were used. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in B-cell-deficient mice (BALB/c MT mice) and wild-type BALB/c mice in two different in vivo situations, vaccination with irradiated larvae and primary infection. In all cases, mice were challenged with subcutaneous inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous tissue normally during immunization; however, their morphological state did not change following challenge inoculation, whereas in wild-type mice the percentage of degranulated eosinophils was markedly increased. From this, it may be deduced that the eosinophil-antibody-B-cell complex is the effector mechanism of protection in vaccinated mice and that its action is fast and takes place in the subcutaneous tissue. In primary infection, the filarial survival and growth was not modified by the absence of B cells. However, no female worm had uterine microfilariae, nor did any mice develop a patent infection. In these mice, concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL-5 and IL-10) cytokines in serum were lower and pleural neutrophils were more numerous. The effects of the MT mutation therefore differ from those in B1-cell-deficient mice described on the same BALB/c background, which reveal a higher filarial recovery rate and microfilaremia. This outlines B2-cell-dependent mechanisms as favorable to the late maturation of L. sigmodontis.Despite new chemotherapy protocols (30), filariae are still a major cause of serious tropical diseases (9, 35); therefore, it is worthwhile to consider a vaccination approach as a complementary measure. We now have a particularly relevant experimental model at our disposal with the rodent filaria Litomosoides sigmodontis. It is the only filarial species able to regularly develop from the infective larvae to the patent phase in the BALB/c mice (18,32). Therefore, the strength of this model is that is allows us to study and modulate the immune reaction during vaccination as well as during primary infection and thus to describe the immune mechanism critical for parasite control.

Immunoglobulin E and Eosinophil-Dependent Protective Immunity to LarvalOnchocerca volvulusin Mice Immunized with Irradiated Larvae

“…It was observed that immunity did not develop in MT mice lacking B cells but did develop in Xid mice which were missing B-1 cells. Similar to the results of this study, MT mice were shown to be more permissive to primary infections with B. malayi (4) and to suppress the development of adaptive immunity to L. sigmodontis (45). Furthermore, B cells were required for clearance of both primary and challenge infections with Brugia pahangi (49).…”

“…Eosinophil degranulation has been observed in mice immunized against L. sigmodontis (45) and in jirds immunized against Acanthocheilonema viteae (7). It was determined in those studies that the larvae were not killed even if eosinophils were present, if the eosinophils did not degranulate (45). In the present study, correlations were found between the elevated numbers of eosinophils and the EPO levels found in the diffusion chambers in IL-5 TG mice and the decrease in parasite survival observed in these mice.…”

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

“…The majority of studies have focused on the L 3 because this is the target that would prevent initial establishment of infection. The fact that during a primary infection, the majority of L 3 are rapidly killed by innate inflammatory processes [probably involving neutrophils (33)] is commonly overlooked. In contrast, a clear consensus has emerged that immunity induced by irradiated L 3 is mediated by activated eosinophils (29,34,35) and that killing of challenge larvae occurs rapidly, with a major reduction in survival before the molt to the fourth stage (27,29).…”

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.…”