[
Acta Trop,
2013]
We recently reported that BmAFI, an anti-inflammatory fraction of Brugia malayi adult worm supports parasite development in the hostile peritoneal cavity (p.c.) of Mastomys coucha through a modified Th2 type of response that includes IL-13 and IgE response and anti-inflammatory IL-10 cytokine milieu. In the present study we investigated IgE related responses such as histamine release and modulation of histamine receptors 1 and 2 (HR1 and HR2) by presensitization with BmAFI of M. coucha infected with B. malayi. Sensitization with BmAFI alone enhanced IgE, histamine and HR2, but decreased HR1. Exposure of these animals to infection produced an IgE response that was inversely related to the parasite burden, and decreased histamine conc., and HR1 and HR2 expression. However, there was an early small increase in HR1 expression for a short period after exposure to infection. As expected, BmAFI sensitization supported parasite survival and development in the hostile p.c. of the host. These findings further establish that BmAFI decreases inflammatory/Th1 response and modulates Th2 responses to favour survival and development of the parasite in the hostile p.c. of the host and that IgE and histamine play an important role in this.
[
Acta Trop,
2011]
Filarial parasites survive by inducing tolerance in host but the antigens and mechanisms involved are not clear. Recently we found that BmAFI, a Sephadex G-200 eluted fraction of Brugia malayi adult worm extract, stimulates IL-10 release from THP-1 cells. In the present study, we determined the SDS-PAGE profile of BmAFI and infective 3rd stage larva (L3), investigated the effect of pre-sensitization of host with BmAFI on the survival and development of L3 in the non-permissive peritoneal cavity (p.c.) of the permissive host Mastomys coucha and in the p.c. of non-permissive Swiss mice, and studied immunological correlates for the observed effects. The parasite development and burden in p.c., was determined in sensitized infected M. coucha and Swiss mice and the release of TGF-, IL-4, IL-10, IL-13, IFN- and NO, cellular proliferative response to Con A and BmAFI and levels of IgG subclasses and IgE were determined in sensitized infected M. coucha. Cellular proliferative response to Con A and BmAFI, mRNA expression of GATA-3, CTLA-4 and T-bet were determined in sensitized Swiss mice. In addition, the parasitological parameter was also studied in BmAFI-sensitized M. coucha exposed to the infection by standard subcutaneous (s.c.) route to assess whether sensitization enhances the intensity of infection. BmAFI-sensitization permitted survival of L3 and their development to adult stage by day 60 p.i. in the p.c. of M. coucha; in non-sensitized animals L3 could molt to L4 only and no parasite could be recovered beyond day 30 p.i. In M. coucha that received infection by s.c. route, pre-sensitization with BmAFI enhanced the microfilaraemia and adult worm recovery. In sensitized Swiss mice L3 could successfully molt to L4 in p.c. with improved recovery of parasite. BmAFI sensitization upregulated TGF- and IL-10 release, IgG1 and IgG2b levels, GATA-3 and CTLA-4 mRNA expression, suppressed the cellular proliferative response and downregulated Con A stimulated response, IgE, IL-13, IFN- and NO responses. Immunoblot analysis showed that the BmAFI antiserum also strongly reacts with some L3 molecules. The results show, for the first time, that sensitization with the anti-inflammatory BmAFI which shares some of its molecules with those in L3, facilitates parasite survival in the non-permissive p.c. of the permissive host M. coucha, render a non-permissive Swiss mouse partially permissive to infection and enhances parasite load in M. coucha receiving the infection through permissive s.c. route by evoking a modified Th2 type of response and anti-inflammatory milieu. In conclusion, the findings suggest that the anti-inflammatory BmAFI fraction facilitates survival of B. malayi infection even in non-permissive environment.
[
Toxicology,
2009]
Mercury is a strong poison that poses significant and immediate hazards to human health. Due to its bioaccumulative properties, even small amounts of the metal are usually very poisonous or lethal when absorbed over long periods of time. Even though the possible dangers of mercury interactions with proteins are well understood, little is known about its uptake and dynamics within an organism. In particular, the concentration and distribution of the metal within a cell or a tissue are only poorly understood. In this study, we describe the application of a recently developed biosensor [Chapleau R.R., Blomberg R., Ford P.C., Sagermann M., 2008. Design of a highly specific and non-invasive biosensor suitable for real-time in vivo imaging of mercury(II) uptake. Protein Sci. 17(4), 614-622] that facilitates unprecedented non-invasive real-time imaging of ionic mercury uptake by an organism under in vivo conditions. Specifically, we here show that mercury ions can be taken up from the environment within minutes by prokaryotic as well as eukaryotic organisms. This rapid uptake can still be detected if the sensor expressing cells are shielded by layers of surrounding tissues suggesting that neither individual cell walls nor tissues provide a serious barrier for the metal. Furthermore, we show that this biosensor is suitable for the direct imaging of mercury uptake through the food chain. Our results suggest that ionic mercury remains available for extended periods of time and can rapidly contaminate surface as well as embedded tissue cells.