Eosinophils Mediate Protective Immunity against Secondary Nematode Infection

Abstract

Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode, Trichinella spiralis, eosinophils play an important, immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of naïve, ablated mice with sera or immunoglobulin from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presences of antibodies in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection.

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

“…Classic in vitro studies described the anti-helminthic actions of eosinophils co-cultured with antigen-specific antibodies and complement(97, 98). These results are supported by in vivo studies showing the essential contribution of eosinophils to mediate protection against reinfection with N. brasiliensis and T. spiralis (99, 100). Furthermore, expression of MHC-II and co-stimulatory molecules on activated eosinophils following infection with T. muris and Brugia malayi (101, 102) suggests that eosinophils might contribute to establish long-term protection against helminths by promoting adaptive immune responses.…”

Immunity to gastrointestinal nematode infections

“…Indeed, both IL-5 and eosinophildeficient mice harbor increased numbers of N. brasiliensis larvae after secondary infection, 89 with similar results during secondary T. spiralis infection. 200 Furthermore, eosinophils negatively regulate Th17 cells 201 and promote the expansion of regulatory T cells in the steady state 198,202 that might affect overall inflammation, illustrating their complex contribution to tissue homeostasis. Similarly, whereas resident intestinal macrophages are mostly suppressive in nature and do not act inflammatory to pathogen stimulation, type 2 cytokines give rise to alternatively activated macrophages that might contribute to the expulsion of certain parasites.…”

Eosinophils in Helminth Infection: Defenders and Dupes

“…In secondary subcutaneous larval infection with Nippostrongylus brasiliensis , increased numbers of larvae migrate to the lungs in IL-5 −/− and ΔdblGATA mice [43]. Similarly, migration of Trichinella spiralis newborn larvae is increased in ablated versus WT mice and muscle larvae burdens are increased in ΔdblGATA mice upon secondary infection [45]. Earlier reports showed that eosinophils attach to newborn T. spiralis via specific antibodies, degranulating and killing the larva.…”

“…Earlier reports showed that eosinophils attach to newborn T. spiralis via specific antibodies, degranulating and killing the larva. Protection by eosinophils and antibodies has been documented in vivo by transferring sera or immunoglobulin from infected mice together with eosinophils to naïve ΔdblGATA mice prior to infection [45]. Although both EPX and MBP are toxic for newborn Trichinella in vitro , mice deficient in EPX or MBP show similar resistance to reinfection that is comparable to wild type mice (WT) (Figure 1).…”

“…Eosinophils are also capable of regulating peripheral B cell homeostasis and proliferation in mice [61]. Although eosinophils are dispensable for the parasite-specific IgM response during primary infection by Strongyloides stercoralis [62], they are required for production of specific IgG2c in Trichinella infection [45]. Taken together, the findings suggest that eosinophils may guarantee their protective effector function by sustaining the cellular source of antibodies that are capable of binding Fc receptors on innate effector cells.…”