Chen J et al. (2016) Food Funct "Extracts of Tsai Tai (Brassica chinensis): enhanced antioxidant activity and anti-aging effects both in vitro and in Caenorhabditis elegans."

Xiang L, Liu X, Huang Z, Zhou X, Xiang Y, Zhang J, Chen J, Liu Y, He X

[Food Funct, 2016]

Tsai Tai is one of the most widely consumed Brassica vegetables in Asian countries because of its good taste and its nutritional benefits. This study evaluated the antioxidant capacity and possible associated health benefits of 3 Tsai Tai (Brassica chinensis) varieties, namely, Hon Tsai Tai, Pak Choi and Choi Sum. The DPPH radical scavenging ability and reducing power assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as an in vivo model for evaluation of beneficial health effects, including antioxidant activity and delayed aging. In vitro, the Hon Tsai Tai extract exhibited higher antioxidant activities than Pak Choi and Choi Sum, and the total phenolic contents were significantly correlated with the DPPH and RP values. In vivo, the three assayed Tsai Tai extracts significantly increased resistance against paraquat-induced oxidative stress with an increase in survival rates from 15% to 28% compared with controls. However, only the extract from Hon Tsai Tai significantly prolonged the lifespan of Caenorhabditis elegans, with an 8% increase in the mean lifespan with respect to controls. Further evidence of antioxidant protection was obtained by assessing ROS production via the DCF assay. The analyses of intracellular SOD activity and MDA content confirmed the existence of an antioxidant protective effect. These results suggest that Tsai Tai might serve as a good source of natural antioxidants, and in particular, Hon Tsai Tai could be explored as a potential dietary supplement to retard aging.

Lawrence RA et al. (2000) Parasitology "Requirements for in vivo IFN-gamma induction by live microfilariae of the parasitic nematode, Brugia malayi."

Allen JE, Gray CA, Lawrence RA

[Parasitology, 2000]

Lymphatic filariasis caused by the parasitic nematode, Brugia malayi, is a chronic human disease immunologically characterized by stimulation of Th2 cells and reduced antigen-specific T cell responses. Single stage intra-peritoneal infections with infective larvae (L3) or adult nematodes induce Th2 cells, while the microfilarial stage (Mf) stimulates IFN-gamma and Mf-specific IgG1, IgG2a, IgG2b, IgG3 and IgM, but not IgE. To investigate whether IFN-gamma is elicited by live Mf in their natural site of infected, mice were infected intravenously. Intravenous infection had a striking effect on the response to Mf and high levels of IgE were induced even in the presence of IFN-gamma. Indeed IgE levels to Mf increased markedly with the number of immunizations, higher doses of Mf and prolonged exposure to Mf suggesting that under conditions of chronic antigen exposure, typical of human disease, Mf will stimulate high levels of IgE. The ability of Mf-induced IFN-gamma to modulate or regulate a pre-existing Th2 response, was investigated by infecting mice initially with adult male worms to induce a Th2 response, followed 14 days later by infection with Mf. Although Mf stimulated IFN-gamma in the presence of male adults, the antibody isotypes elicited did not reflect IFN-gamma induction and IgG1 and IgE dominated the response. Although it cannot be discounted that IFN-gamma induction by Mf may act locally as an inflammatory mediator or modulator of Th2 cells, these data suggest that Mf-stimulated IFN-gamma does not have a profound effect overall on progression of the Th2-dominated immune response to filarial infection.

Rao UR et al. (1987) Immunol Cell Biol "Complement activation by eggs and microfilariae of filarial parasites."

Rao UR, Subrahmanyam D, Chandrashekar R

[Immunol Cell Biol, 1987]

The complement of fresh normal rat serum was activated by filarial eggs and microfilariae (mf). C3 was deposited on the surface of Litomosoides carinii, Brugia pahangi, Brugia malayi and Dipetalonema viteae as seen by immunofluorescence. Intra-uterine and in vitro-derived mf did not bind C3. In contrast, C3 bound to the blood-derived mf of B. pahangi and B. malayi as well as exsheathed mf of L. carinii and B. malayi. Significant consumption of complement was observed with eggs of all filarial species, as well as sheathed mf of B. pahangi, B. malayi and exsheathed mf of L. carinii and B. malayi. These experiments indicated that complement was activated by filarial parasites via the alternative pathway. The bound complement promoted neutrophil-mediated adherence and cytotoxicity.

Beerntsen BT et al. (2007) J Med Entomol "Response of Armigeres subalbatus (Diptera: Culicidae) to intraperitoneally isolated Brugia spp. microfilariae."

Lowery RJ, Beerntsen BT

[J Med Entomol, 2007]

The relationship between mosquito and parasite involves a delicate balance that is influenced not only by the mosquito but also by parasite determinants. Using the biologically and morphologically similar parasites Brugia malayi and Brugia pahangi and the mosquito Armigeres subalbatus (Coquillett) (Diptera: Culicidae), it should be possible to dissect out the key elements involved in initiating or avoiding an immune response, known as melanotic encapsulation, because in this mosquito B. malayi microfilariae (mf) are melanized and destroyed, but B. pahangi mf develop normally into infective-stage larvae. Because of limitations in isolating sufficient mf from the circulation of an infected mammalian host, Brugia spp. mf that can be obtained in large numbers from the peritoneal cavity of an infected host were tested to ascertain the immune response of Ar. subalbatus to this source of mf. Results indicate that the immune response of Ar. subalbatus against intraperitoneal (i.p.) Brugia spp. mf mimics that which is observed when this mosquito is exposed to mf-infected animals, indicating that i.p. mf are similar to those mf that circulate naturally in the blood of the vertebrate host. Therefore, the i.p. mf should serve as an excellent source of material for genomic and proteomic studies designed to analyze the role of the parasite in influencing the immune response of the mosquito.

Simons JE et al. (2010) Parasite Immunol "Absence of regulatory IL-10 enhances innate protection against filarial parasites by a neutrophil-independent mechanism."

Lawrence RA, Simons JE, Gray CA

[Parasite Immunol, 2010]

Brugia malayi causes the major tropical disease, lymphatic filariasis. Chronicity of disease is associated with generation of regulatory cells secreting IL-10 and/or TGF-beta. Previous work has shown that the rate of microfilariae (Mf) clearance from the blood is mouse strain-dependent. Here, we show that IL-10 plays an important role in preventing the clearance of Mf. Indeed, anti-IL-10 antibody treatment increases the rate of Mf clearance from the bloodstream in both rapid-Mf-clearing CBA/Ca and slow-clearing C57Bl/6 mice. In addition, IL-10(-/-) mice implanted intraperitoneally with Mf-producing adult nematodes have significantly lower Mf, but not adults, in comparison with wild-type mice at 3 weeks post-implantation (p.i.). Clearance of Mf from the peritoneal cavity of IL-10(-/-) mice is associated with a dramatic infiltration of neutrophils. Furthermore, rapid-Mf-clearing CBA/Ca mice have a dramatic blood neutrophilia at 24 h p.i., whereas slow-clearing C57Bl/6 mice show no such neutrophilia. Thus, neutrophils may play a role as effector cells in microfilarial infection. We therefore treated mice with anti-granulocyte antibody to abolish neutrophil recruitment during Mf infection i.v. Although anti-granulocyte treatment severely depleted neutrophils, it did not significantly reduce the rate of B. malayi Mf clearance either during primary infection or during a challenge following antigen sensitization.

Edwards MK et al. (1990) Trop Med Parasitol "Antigenic and dynamic properties of the surface of Onchocerca microfilariae."

Busto P, James ER, Edwards MK, Carlow CK, Philipp M

[Trop Med Parasitol, 1990]

We analyzed the antigenicity and stability of the surface of skin microfilariae (mf) of Onchocerca cervicalis, a horse parasite. These mf express antigens on their surface that are cross-reactive with the cattle parasite O. lienalis and with the human parasite O. volvulus. The surface of living O. cervicalis mf was radioiodinated using Iodogen and the labeled components were solubilized in buffers containing sodium dodecyl sulphate (SDS), or extracted with the milder detergent octyl-beta-D-glucopyranoside (OGP). Electrophoresis of this material showed seven prominent bands, one of which (14 kDa) was specifically precipitated by antisera from rabbits immunized with mf from either O. cervicalis, O. lienalis, or O. volvulus, and by human sera obtained from infected individuals in Chiapas, Mexico. Other components were precipitated by either the rabbit or the human sera. In addition, antisera from mice immunized with O. cervicalis mf bound specifically to the surface of freeze-thawed uterine O. lienalis and O. volvulus mf as detected by immunofluorescence. This fluorescence was lost from the surface of O. cervicalis mf in a temperature-dependent fashion. Live mf incubated on ice with mouse anti-mf antisera and secondary FITC-GAM, showed uniform surface fluorescence. When these mf were incubated at 37 degrees C, but not at 0 degrees C, the fluorescent pattern changed with time. First, small non-fluorescent patches arose, followed by an increasingly wide belt devoid of fluorescence, and finally, no visible fluorescence. These changes in the mf surface suggest potential mechanisms for immune evasion by filarial parasites.

Lu YR et al. (1991) Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi "[Variations in reproductive capacity, gonotrophic cycle and longevity of Anopheles sinensis infected by Brugia malayi larvae]."

Lu YR, Su SZ

[Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 1991]

Under the experimental conditions of 26 +/- 10 degrees C, relative humidity 70-80%, 100 +/- 20 Lux and photoperiod 16 hours/day and using a membrane feeding method, the development of filarial larvae and the variations in reproductive capacity, gonotrophic cycle and longevity of An. sinensis infected with microfilariae of Brugia malayi were observed. The infection rate and infection intensity of filarial larvae in An. sinensis increased with the microfilarial density in the blood meal from 50 to 150 mf/20 microliters. The mature rate and IEI decreased when the density rose to 200 mg/20 microliters. The concentration ratio of mf in blood by An. sinensis was 1.2-1.4. In the 3rd gonotrophic cycle, the feeding ratio of infected mosquitoes became lower when the mf density rose to 150 mf/20 microliters, but the infection of filarial did not affect the number of oviposition, the regularity of egg-production activity and the hatching rate of eggs, while the quantity of egg-production increased when the mf density was 150 mf/20 microliters. The egg-production rate, and gonotrophic cycle were not basically influenced by filarial larvae infection. The multifeeding ratio was 16.7-48.4% in An. sinensis. The longevity of An. sinensis was extended by infection with mf density of 100 mf/20 microliters and shortened in infection with mf density of 200 mf/20 microliters. The authors conclude that "Brugia malayi-Anopheles sinensis" is a highly adapted "pathogen-vector" system.

Soumbey-Alley E et al. (2004) J Med Entomol "Uptake of Onchocerca volvulus (Nematoda: Onchocercidae) by Simulium (Diptera: Simuliidae) is not strongly dependent on the density of skin microfilariae in the human host."

Boatin BA, Remme JH, Habbema JD, Nagelkerke NJ, Basanez MG, de Vlas SJ, Soumbey-Alley E, Borsboom GJ, Bissan Y

[J Med Entomol, 2004]

The relation between the number of microfilariae (mf) ingested by host-seeking vectors of human onchocerciasis and skin mf load is an important component of the population biology of Onchocerca volvulus, with implications for disease control and evaluation of the risk of transmission recrudescence. The microsimulation model ONCHOSIM has been used to assess such risk in the area of the Onchocerciasis Control Program (OCP) in West Africa, based on a strongly nonlinear relation between vector mf uptake and human mf skin density previously published. However, observed levels of recrudescence have exceeded predictions, warranting a recalibration of the model. To this end, we present the results of a series of fly-feeding experiments carried out in savanna and forest localities of West Africa. Flies belonging to Simulium damnosum s.s., S. sirbanum, S. soubrense, and S. leonense were fed on mf carriers and dissected to assess the number of ingested mf escaping imprisonment by the peritrophic matrix (the number of exo-peritrophic mf), a predictor of infective larval output. The method of instrumental variables was used to obtain (nearly) unbiased estimates of the parameters of interest, taking into account error in the measurement of skin mf density. This error is often neglected in these types of studies, making it difficult to ascertain the degree of density-dependence truly present in the relation between mf uptake and skin load. We conclude that this relation is weakly (yet significantly) nonlinear in savanna settings but indistinguishable from linearity in forest vectors. Exo-peritrophic mf uptake does not account for most of the density dependence in the transmission dynamics of the parasite as previously thought. The number of exo-mf in forest simuliids is at least five times higher than in the savanna vectors. Parasite abundance in human onchocerciasis is regulated by poorly known mechanisms operating mainly on other stages of the lifecycle.

Semnani RT et al. (2008) J Immunol "Induction of TRAIL- and TNF-alpha-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi."

Skinner JA, Venugopal PG, Chien D, Mahapatra L, Chaussabel D, Meylan F, Dorward DW, Nutman TB, Semnani RT, Siegel RM

[J Immunol, 2008]

Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24-96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, whereas mf exposure did not induce apoptosis in macrophages. Interestingly, 48-h exposure of DC to mf induced mRNA expression of the proapoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. The mf also induced gene expression of BH3-interacting domain death agonist and protein expression of cytochrome c in DC; mf-induced cleavage of BH3-interacting domain death agonist could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion.

Semnani RT et al. (2003) J Immunol "Brugia malayi microfilariae induce cell death in human dendritic cells, inhibit their ability to make IL-12 and IL-10, and reduce their capacity to activate CD4+ T cells."

Sabzevari H, Kubofcik J, Gilden JK, Zhou J, Nutman TB, Semnani RT, Liu AY

[J Immunol, 2003]

Parasite Ag-specific T cell unresponsiveness and diminished IFN-gamma production are immunologic hallmarks of patent infection with lymph-dwelling filarial nematodes. Although this diminished responsiveness is directed primarily against the intravascular microfilarial (MF) parasite stage and mediated in part by reduced APC function, the mechanisms involved are not fully understood. In this report, we demonstrate that human dendritic cells (DC) exposed to live MF up-regulate both the cell surface and gene expression of CD54 (ICAM-1). Moreover, live MF result in a 3-fold increase in DC death compared with MF-unexposed DC, primarily due to apoptosis. Notably, microarray and real-time RT-PCR data indicate that live MF concurrently up-regulate mRNA expression of proinflammatory molecules such as IL-8, RANTES, IL-1alpha, TNF-alpha, and IL-beta in DC, the presence of which is also detected at the protein level, while inhibiting the production of IL-12 (p40 and p70) and IL-10. Soluble excretory-secretory products from live MF diminished IL-12 and IL-10 production and induced DC death, although to a lesser degree. Moreover, exposure of DC to live MF resulted in a decrease in the ability of DC to promote CD4(+) T cell production of IFN-gamma and IL-5. Our findings clearly suggest that the interaction between live MF and DC is complex but contributes to the hyporesponsiveness and parasite persistence associated with the MF(+) state in the infected human. These data further suggest that MF induce an orchestrated response in APC that leads to a diminished capacity to function appropriately, which in turn has significant consequences for CD4(+) T cells.