Mice immunized with irradiated Onchocerca volvulus third-stage larvae developed protective immunity. Eosinophil levels were elevated in the parasite microenvironment at the time of larval killing, and measurements of total serum antibody levels revealed an increase in the immunoglobulin E (IgE) level in immunized mice. The goal of the present study was to identify the role of granulocytes and antibodies in the protective immune response to the larval stages of O. volvulus in mice immunized with irradiated larvae. Immunity did not develop in mice if granulocytes, including both neutrophils and eosinophils, were eliminated, nor did it develop if only eosinophils were eliminated. Moreover, larvae were killed in naïve interleukin-5 transgenic mice, and the killing coincided with an increase in the number of eosinophils and the eosinophil peroxidase (EPO) level in the animals. To determine if EPO was required for protective immunity, mice that were genetically deficient in EPO were immunized, and there were no differences in the rates of parasite recovery in EPO-deficient mice and wild-type mice. Two mouse strains were used to study B-cell function; MT mice lacked all mature B cells, and Xid mice had deficiencies in the B-1 cell population. Immunity did not develop in the MT mice but did develop in the Xid mice. Finally, protective immunity was abolished in mice treated to eliminate IgE from the blood. We therefore concluded that IgE and eosinophils are required for adaptive protective immunity to larval O. volvulus in mice.Infection of humans with the filarial worm Onchocerca volvulus results in a spectrum of disease states ranging from mild to hyperreactive disease. In addition, there are individuals who are considered immunologically resistant to the infection, based on the fact that they live in an endemic area and are free of infection and disease. Individual immune responses appear to be responsible for the different disease states, and roles have been attributed to Th1 cells, Th2 cells, antibodies, and granulocytes in the different disease presentations (24). Specific mechanisms of protective immunity have been identified in vitro with human cells and serum, and it has been shown that eosinophils and neutrophils adhere to and kill larval O. volvulus in the presence of serum or complement (9,27,41).O. volvulus has a very limited host range, infecting only humans and chimpanzees; therefore, other animal models have been utilized to study immunity to this infection. It has been observed that cattle immunized with irradiated Onchocerca ochengi third-stage larvae (L3) were protected against challenge infection, based on greatly reduced burdens of adult worms in the immunized animals (1). In order to generate a more practical way to study immunity to the larval stages of O. volvulus, a mouse model was developed. L3 were implanted subcutaneously in diffusion chambers to allow efficient recovery of parasites and to permit analysis of the parasite's microenvironment. Larvae survived and grew at the same rate when they ...
Asthma and helminth infections induce similar immune responses characterized by the presence of peripheral blood eosinophilia and elevated serum IgE levels. Epidemiological surveys have reported either increases or decreases in the development of atopic diseases and asthma based on the prevalence of helminth infections in the population. The aim of this study was to determine if a pre-existing helminth infection would increase or decrease subsequent allergic responses to an unrelated allergen in the lungs. BALB/cByJ mice were infected with the nematode parasite Strongyloides stercoralis prior to ovalbumin (OVA) immunization and intratracheal challenge. Bronchoalveolar lavage (BAL) and fluid (BALF) were collected 3 days post-challenge and cellular and humoral immune responses were measured. Intracellular cytokine staining revealed increased IL-4 and IL-5 producing cells in BAL from mice infected with S. stercoralis before OVA sensitization. Increased IL-5 protein levels and decreased IFN-gamma protein levels were also observed in the BALF. There was, however, no increase in airway eosinophil accumulation in mice infectd with parasites before sensitization with OVA as compared to mice exposed to OVA alone. Furthermore, eotaxin levels in the lungs induced by OVA was suppressed in mice infected with the parasite before OVA sensitization. The development of OVA specific IgE responses in BALF was also impaired in mice infected with the parasite before sensitization with OVA. These results suggest that a pre-existing helminth infection may potentiate a systemic Type 2-type response yet simultaneously suppress in the lungs allergen-specific IgE responses and eotaxin levels in response to subsequent exposure to allergens.
The protein kinase encoded by the Tpl2 proto-oncogene regulates ERK activation and cytokine gene expression in macrophages in response to LPS and TNF-α. In this study we show that OVA-immunized Tpl2−/− mice express high levels of IgE and develop more severe bronchoalveolar eosinophilic inflammation than Tpl2+/+ controls, when challenged with OVA intranasally. Bronchoalveolar exudates and supernatants of OVA-stimulated splenocytes from immunized Tpl2−/− mice express elevated levels of IL-4 and IL-5, suggesting that Tpl2 ablation promotes the Th2 polarization of the T cell response. Anti-CD3 stimulation of CD4+ T cells of wild-type and Tpl2 knockout mice revealed that Tpl2 ablation gives rise to a cell autonomous T cell defect that is primarily responsible for the Th2 polarization of the T cell response to Ag. This observation was further supported by experiments addressing the expression of Th1 and Th2 cytokines in OVA-stimulated mixed cultures of CD4+ T cells from Tpl2+/+/OT2 or Tpl2−/−/OT2 mice and dendritic cells from Tpl2+/+ or Tpl2−/− mice. Further studies revealed that Th1 cells express significantly higher levels of Tpl2 than Th2 cells. As a result, Tpl2−/− Th1 cells exhibit a stronger defect in ERK activation by anti-CD3 than Th2 cells and express low levels of T-bet. Given that the development of Th1 and Th2 cells depends on positive feedback signals from the T cells, themselves, the functional defect of the Tpl2−/− Th1 cells provides a mechanistic explanation for the T cell autonomous Th2 polarization in Tpl2−/− mice.
Gold nanoparticles (AuNPs) are useful for diagnostic and biomedical applications, mainly because of their ease in preparation and conjugation, biocompatibility, and size-dependent optical properties. However, bare AuNPs do not possess specificity for targets. AuNPs conjugated with DNA aptamers offer specificity for various analytes, such as proteins and small molecules/ions. Although DNA aptamers themselves have therapeutic and target-recognizing properties, they are susceptible to degradation in vivo. When DNA aptamers are conjugated to AuNPs, their stability and cell uptake efficiency both increase, making aptamer-AuNPs suitable for biomedical applications. Additionally, drugs can be efficiently conjugated with DNA aptamer-AuNPs to further enhance their therapeutic efficiency. This review focuses on the applications of DNA aptamer-based AuNPs in several biomedical areas, including anticoagulation, anticancer, antibacterial, and antiviral applications.
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